hematopoiesis histology-maha hammady.pptx

HEMATOPOIESIS
By/ Maha Hammady Hemdan
MBBCh- MMSc - Faculty of Medicine, Alexandria University. 2015

3
HEMATOPOIESIS
Hematopoiesis (is also called
hemopoiesis, hematogenesis and
hemogenesis)– the formation of
blood cellular components –
occurs during embryonic
development (prenatal
hemopoiesis) and throughout
adulthood (postnatal
hemopoiesis) to produce and
replenish the blood system.
HEMOPOIESIS

Prenatal Hemopoiesis
Prenatally, hemopoiesis is subdivided into four phases: mesoblastic, hepatic,
splenic, and myeloid.
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phase Mesodermal phase Hepatic phase Splenic phase Myeloid phase
Site the mesoderm of the yolk sac Liver Spleen Bone marrow
Timing Around 2 weeks after
conception
6th week till birth 14th week (2nd
trimester) till birth
end of the 2nd
trimester till
adulthood
events mesenchymal cells aggregate
into clusters known as blood
islands. The peripheral cells of
these islands form the vessel
wall, and the remaining cells
become erythroblasts, which
differentiate into Primitive
erythrocytes
The circulating
erythrocytes still
have nuclei, and
nonerythroid
progenitors appear
by the eighth week
of gestation.
As the skeletal
system continues to
develop, the bone
marrow
assumes an
increasing role in
blood cell formation.
Cells
produced
Primitive erythrocytes
(nucleated erythrocytes
containing HbF (fetal
hemoglobin), macrophages
Erythrocytes,
granulocytes,
monocytes
Lymphocytes All blood cell types
PRENATAL HEMOPOIESIS

prenatal hemopoiesis postnatal hemopoiesis
PRENATAL HEMOPOIESIS

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The monophyletic theory of hemoposis
The monophyletic theory of hematopoiesis suggests that all blood cells, regardless of their
lineage (erythroid, myeloid, lymphoid), originate from a common precursor cell. This
theory posits that there is a single, unifying lineage for hematopoiesis, and the diverse
blood cell types differentiate from a shared ancestor. Key points regarding the
monophyletic theory include:
1. Common Origin: According to the monophyletic theory, all blood cells, including red
blood cells, white blood cells, and platelets, arise from a common hematopoietic stem cell
(HSC).
2. Pluripotent Stem Cells: Hematopoietic stem cells are considered pluripotent, meaning
they can give rise to a variety of differentiated cell types.
3. Lineage Commitment: The monophyletic theory acknowledges that as hematopoietic
stem cells differentiate, they undergo lineage commitment, leading to the formation of
distinct cell lineages such as erythroid, myeloid, and lymphoid.
4. Hierarchical Development: The theory suggests a hierarchical development of blood
cells, starting from the pluripotent hematopoietic stem cell and branching into committed
progenitors that eventually differentiate into specialized blood cell types.
While the monophyletic theory provides a unified framework for hematopoiesis, it is
essential to note that ongoing research may refine our understanding of the intricacies of
blood cell development. This theory serves as a foundational concept in hematology,
influencing research, diagnostics, and therapeutic interventions related to blood disorders
and diseases.

Stem Cells, Progenitor Cells, and Precursor Cells
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1-Stem Cells:
Definition:
Stem cells are undifferentiated cells with the unique ability to divide and give rise
to both identical stem cells (self-renewal) and differentiated, specialized cell types.
characteristics:
All blood cells arise from pluripotential hemopoietic stem cells (PHSCs) (also
known as hemopoietic stem cells [HSC]), which account for about 0.01% of the
nucleated cell population of bone marrow. They are usually amitotic but may
undergo bursts of cell division,giving rise to
-more PHSCs
-as well as to two types of multipotential hemopoietic stem cells (MHSCs), also
known as multipotent progenitors. The two populations of MHSCs are colony-
forming unit– lymphocyte (CFU-Ly), also known as common lymphoid
progenitors, and CFU-GEMM (colonyforming unit-granulocyte, erythrocyte,
monocyte, megakaryocyte), also known as common myeloid progenitors.
Both PHSCs and MHSCs resemble lymphocytes and constitute a small fraction of
the null-cell population of circulating blood.
Stem cells are commonly in the G0 stage of the cell cycle but can be driven into
the G1 stage by various growth factors and cytokines.

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2- Progenitor Cells :
Definition:
Progenitor cells are partially differentiated cells derived from stem cells, committed
to a specific lineage, and with limited differentiation potential.
characteristics:
-resemble small lymphocytes
-They are unipotential (i.e., committed to forming single cell line, such as
eosinophils).
-Their mitotic activity and differentiation are controlled by specific hemopoietic
factors.
-These cells have only limited capacity for self-renewal.

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3- Precursor cells:
Definition:
Precursor cells are cells that precede the final, fully mature cell type in the process
of differentiation.
characteristics:
-have specific morphological characteristics that permit them to be recognized as
the first cell of a particular cell line.
-Precursor cells undergo cell division and differentiation, eventually
-giving rise to a clone of mature cells.
-Incapable of self-renewal

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Hematopoietic growth factors are signaling molecules that regulate the
growth, development, and differentiation of blood cells in the process of
hematopoiesis. These factors play a crucial role in maintaining a balanced
and functional blood cell population. Here's a concise account:
- Hematopoietic growth factors are critical for maintaining homeostasis in
the blood system by regulating the production of different blood cell types.
- Their therapeutic applications are widespread, including the treatment of
anemia, neutropenia, and thrombocytopenia associated with various medical
conditions and treatments.
Hemopoietic Growth factors

POSTNATAL HEMOPOIESIS
A-ERYTHROPOIESIS

A-ERYTHROPOIESIS
Pluripotent Hematopoietic Stem Cells (PHSC)
Common Myeloid Progenitor; Colony Forming Unit
Granulocyte,erythrocyte,monocyte, Megakaryocyte (CFU-GEMM)
Burst Forming Unit Erythrocyte (BFU-E)
Colony Forming Unit –Erythrocyte (CFU-E)
Proerythroblast
Basophilic Erythroblast
Polychromatophilic Erythroblast
Orthochromatophilic Erthyroblast
Reticulocyte
Erythrocyte
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A-Erythropoiesis Erythropoiesis, the formation of red blood cells,
is under the control of several cytokines, namely steel factor, interleukin-3,
interleukin-4, and erythropoietin

A-ERYTHROPOIESIS
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1-Proerythroblast
1. Size and Shape:
- Proerythroblasts are relatively large cells,
typically ranging in size from 14 to 20
micrometers in diameter.
-they re the first microscopically recognizable
precursor cells.
- They exhibit a round or slightly oval shape.
2. Nucleus:
- The nucleus of a proerythroblast is large and
occupies a significant portion of the cell.
- It is typically round
3. Mitotic Ability:
- Proerythroblasts are actively dividing cells.
They undergo several rounds of mitosis to
generate a pool of cells that will further
differentiate into erythrocytes.
4. Nucleoli:
- many nucleoli may be visible within the
nucleus of a proerythroblast reflecting the cell's
high metabolic activity during this phase of
erythropoiesis.
5. Cytoplasm:
- The cytoplasm of proerythroblasts is light
basophilic
- The cytoplasm contains a developing network
of organelles, including rough endoplasmic
reticulum (rER), many polysomes and
mitochonria.
The proerythroblast (A) and (P) is the earliest identifiable
erythroid precursor in the bone marrow.
Electron micrograph of a
proerythroblast, displaying its
nucleus as well as the perinuclear
cytoplasm. Note that the
nucleoplasm is relatively smooth in
appearance and that the cytoplasm
is rich in mitochondria and free
ribosomes, indicating that the cell is
active in protein synthesis (×14000).
nuc, Nucleolus.

A-ERYTHROPOIESIS
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2-Basophillic erythroblast
1. Size and Shape:
-Basophilic erythroblasts are typically larger
than mature red blood cells, ranging in size from
12 to 17 micrometers in diameter.
-They exhibit a round or slightly oval shape,
2. Nucleus:
-The nucleus of a basophilic erythroblast is
relatively large and round, occupying a
significant portion of the cell.
-The nuclear chromatin is still visible, but it is
starting to condense as the cell progresses
toward maturity.
3. Mitotic Ability:
-Basophilic erythroblasts retain the ability to
undergo mitosis
4. Nucleoli:
-One or more nucleoli may be present in the
nucleus of basophilic erythroblasts; reflecting
the cell's high metabolic activity during this
stage of erythropoiesis.
5. Cytoplasm:
-The cytoplasm of basophilic erythroblasts is
basophilic
-It contains a developing network of organelles,
including many rough endoplasmic reticulum
(rER), polysomes and mitochondria, crucial for
hemoglobin production.
-some hemoglobin is present.
The basophilic erythroblast (B)
Electron micrograph of
a basophilic erythroblast
https://stock.adobe.com/im
ages/basophilic-
erythroblast/290399442
B

A-ERYTHROPOIESIS
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3-Polychromatophilic erythroblast
1. Size and Shape:
-Polychromatophilic erythroblasts are smaller than earlier
basophilic stages, typically ranging from 12 to 15 micrometers in
diameter.
2. Nucleus:
-The nucleus of a polychromatophilic erythroblast is still present,
but it is becoming more condensed as the cell progresses toward
maturity. (checkboard pattern)
-Chromatin becomes more compact
3. Mitotic Ability:
-Unlike earlier stages, polychromatophilic erythroblasts have
reduced mitotic activity.
-The cell is shifting focus from cell division to the synthesis of
hemoglobin, a process critical for the ultimate function of red
blood cells.
4. Nucleoli:
-Nucleoli are generally not visible in polychromatophilic
erythroblasts, indicating a decrease in the synthesis of ribosomal
RNA.
5. Cytoplasm:
-The cytoplasm of polychromatophilic erythroblasts is described
as "polychromatophilic" due to its ability to take up both acid
and basic stains.
-This is a result of the cell actively producing and accumulating
hemoglobin, which imparts a bluish-gray tint to the cytoplasm.
-Mitochondria become more prominent in the cytoplasm,
supporting the energy demands associated with hemoglobin
synthesis.
The polychromatophilic erythroblast (p) and late polychromatophilic
erythroblast (LP) , note the checkboard appearance of the nucleus
P
LP
LP

A-ERYTHROPOIESIS
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4-Orthochromatophilic erythroblast
1.Size and Shape:
-Orthochromatophilic erythroblasts are relatively
small, with a diameter ranging from 8 to 12
micrometers.
2. Nucleus:
-The nucleus of orthochromatophilic
erythroblasts is markedly condensed and the
nucleus is positioned eccentrically (or is being
extruded)
3. Mitotic Ability:
-Orthochromatophilic erythroblasts have lost
their ability to undergo mitosis.
-This irreversible exit from the cell cycle is a
characteristic feature of cells committed to
becoming mature red blood cells.
4. Nucleoli:
-Nucleoli are entirely absent in
orthochromatophilic erythroblasts, indicating a
cessation of active ribosomal RNA synthesis.
5. Cytoplasm:
-The cytoplasm of orthochromatophilic
erythroblasts is heavily laden with hemoglobin,
giving it a pinkish hue.
-This stage is often referred to as the
"polychromatophilic normoblast" due to the
residual staining properties of the cytoplasm.
LM of the Orthochromatophilic erythroblast
Electron micrograph of an
orthochromatophilic
erythroblast. Observe that
the nucleus possesses a lot
of heterochromatin

A-ERYTHROPOIESIS
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4-Orthochromatophilic erythroblast
1.Size and Shape:
-Orthochromatophilic erythroblasts are relatively
small, with a diameter ranging from 8 to 12
micrometers.
2. Nucleus:
-The nucleus of orthochromatophilic
erythroblasts is markedly condensed and the
nucleus is positioned eccentrically (or is being
extruded)
3. Mitotic Ability:
-Orthochromatophilic erythroblasts have lost
their ability to undergo mitosis.
-This irreversible exit from the cell cycle is a
characteristic feature of cells committed to
becoming mature red blood cells.
4. Nucleoli:
-Nucleoli are entirely absent in
orthochromatophilic erythroblasts, indicating a
cessation of active ribosomal RNA synthesis.
5. Cytoplasm:
-The cytoplasm of orthochromatophilic
erythroblasts is heavily laden with hemoglobin,
giving it a pinkish hue.
-This stage is often referred to as the
"polychromatophilic normoblast" due to the
residual staining properties of the cytoplasm.
Electron micrograph of an orthochromatophilic
erythroblast (normoblast). The cell is shown just before
extrusion of the nucleus. The cytoplasm contains a group of
mitochondria
located below the nucleus and small cytoplasmic vacuoles. The
cytoplasm is relatively dense because of its hemoglobin content. The
fi ne, dense particles scattered in the cytoplasm are ribosomes.
10,000.
(Courtesy of Dr. Dorothea Zucker-Franklin.)

https://cob.silverchair-
cdn.com/cob/content_public/journal/jcs/7
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177.pdf?Expires=1705071081&Signatur
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A-ERYTHROPOIESIS
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5-Reticulocyte
1.Size and Shape:
-Reticulocytes are small, with a diameter
ranging from 7 to 8 micrometers.
2. Nucleus:
-Mature reticulocytes lack a nucleus, making
them one of the few mammalian cells that
function without a nucleus.
3. Mitotic Ability:
-Reticulocytes do not have the ability to undergo
mitosis as they have already exited the cell cycle
during earlier stages of erythropoiesis.
4. Nucleoli:
-Reticulocytes, having expelled their nucleus,
also lack nucleoli. They are essentially
enucleated cells
5. Cytoplasm:
-The cytoplasm of reticulocytes contains
remnants of ribosomal RNA, forming a network
of reticulum or reticular material when stained
with cresyl blue. This gives reticulocytes their
name.
-The cytoplasm is rich in hemoglobin
-Under electron microscopy, the cytoplasm of
reticulocytes shows a mesh-like appearance,
representing the residual ribosomal material.
-Mitochondria are still present but decrease in
number compared to earlier erythroblastic stages
Blood film using cresyl blue stain showing the retuclocytes
Electron micrograph of a polychromatophilic
erythrocyte (reticulocyte). The nucleus is no
longer present, and the cytoplasm
shows the characteristic fi mbriated processes
that occur just after
nuclear extrusion. Mitochondria are still present,
as are early and late endosomes
and ribosomes. 16,500.

A-ERYTHROPOIESIS
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6-Mature Erythrocyte
1.Size and Shape:
-Mature erythrocytes are small, with a diameter of about 7-8
micrometers.
-They are biconcave discs, resembling a donut without a hole. This
shape maximizes the surface area for gas exchange and flexibility to
navigate through narrow capillaries.
2. Nucleus:
-Mature erythrocytes lack a nucleus. The expulsion of the nucleus
during the final stages of erythropoiesis increases the cell's capacity to
carry oxygen and allows for a flexible and deformable shape.
3. Mitotic Ability:
-Erythrocytes cannot undergo mitosis or any form of cellular division.
-They are unable to repair themselves and have a finite lifespan,
typically circulating for about 120 days before being removed by the
spleen and liver.
4. Nucleoli:
-As mature erythrocytes are devoid of a nucleus, they also lack
nucleoli
5. Cytoplasm:
-The cytoplasm of mature erythrocytes primarily consists of
hemoglobin, the iron-containing protein responsible for oxygen
binding and transport.
-The absence of most organelles, including mitochondria, reduces
metabolic demands, allowing the cell to focus on its oxygen-carrying
function.
•Electron micrographs of mature erythrocytes reveal a homogenous
cytoplasm with no discernible organelles.
•The biconcave shape is evident, maximizing the surface area-to-
volume ratio for efficient gas exchange.

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The erythroblastic island. (A) Erythroblastic island in E13.5 fetal
liver. The cytoplasmic extensions of the central macrophage
(stained with the F4/80 antibody) (brown) are surrounding
erythroid cells at various stages of differentiation. (B) Schematic
drawing of an erythroblastic island.
https://perspectivesinmedicine.cshlp.org/content/3/4/a011601.full
A-ERYTHROPOIESIS

B-THROMBOPOIESIS

B-THROMBOPOIESIS
Granulocyte,erythrocyte,monocyte, Megakaryocyte (CFU-
GEMM)
Megakaryocytic-erythroid progenitors (MEPs)
Colony Forming Unit –Megakaryocyte (CFU-Meg)
Megakaryoblast
Megakaryocyte
proplatelets
Platelets
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B-Thrombopoiesis
The formation of platelets is under the control of thrombopoietin, which induces the development and
proliferation of giant cells known as megakaryoblasts

27
1-Megakaryoblast
1.Size and Shape:
-Megakaryoblasts are relatively large cells, typically larger than other
hematopoietic precursors, with a diameter ranging from 25 to 40 micrometers.
-They exhibit a round or slightly oval shape.
2. Nucleus:
-Megakaryoblasts have a single, large, and lobulated nucleus.
-The nucleus may exhibit prominent nucleoli and is characterized by its irregular
contour.
3. Mitotic Ability:
-Megakaryoblasts undergo mitosis, dividing to produce more precursor cells in the
megakaryocytic lineage.
-They are considered the proliferative stage leading to the formation of
megakaryocytes.
-These cells undergo endomitosis, whereby the cell does not divide (no
karyokinesis nor cytokinesis); instead, it becomes larger, and the nucleus becomes
polyploid, as much as 64 N
4. Nucleoli:
-Megakaryoblasts may have one or more prominent nucleoli within the nucleus.
-Nucleoli are involved in ribosomal RNA synthesis, reflecting the cell's high
metabolic activity during this phase of megakaryopoiesis
5. Cytoplasm:
-The cytoplasm of megakaryoblasts is basophilic
-It contains developing organelles, such as rough endoplasmic reticulum (rER),
indicative of active protein synthesis, including the production of platelet
components
-well developed Golgi apparatus, numerous mitochondria, abundant RER, and
many lysosomes
B-THROMBOPOIESIS

28
1-Megakaryoblast B-THROMBOPOIESIS

29
2-Megakaryocyte
1.Size and Shape:
-Megakaryocytes are among the largest cells in the bone marrow, with a
diameter ranging from 30 to 100 micrometers.
-They are typically multi-lobulated and have a distinctive irregular shape.
2. Nucleus:
-Megakaryocytes are characterized by having multiple nuclei, ranging from a
few to several dozen.
-The nuclei are often lobulated and located at the periphery of the cell, giving
it a distinctive appearance.
3. Mitotic Ability:
-Mature megakaryocytes, also known as polyploid megakaryocytes, undergo
endomitosis, a process where the cell replicates its DNA without subsequent
cell division.
-This results in a cell with multiple sets of chromosomes and contributes to the
formation of a large, multinucleated cell.
4. Nucleoli:
-Megakaryocytes may have multiple nucleoli associated with each nucleus.
-Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's high
metabolic activity.
5. Cytoplasm:
metabolic activity.
-The cytoplasm of megakaryocytes is abundant
Megakaryocytes are located next to sinusoids, into
which they protrude their cytoplasmic processes. These
cytoplasmic processes fragment along complex, narrow
invaginations of the plasmalemma, known as demarcation
channels, into clusters of proplatelets. Shortly
B-THROMBOPOIESIS

30
2-Megakaryocyte
1.Size and Shape:
-Megakaryocytes are among the largest cells in the bone marrow, with a
diameter ranging from 30 to 100 micrometers.
-They are typically multi-lobulated and have a distinctive irregular shape.
2. Nucleus:
-Megakaryocytes are characterized by having multiple nuclei, ranging from a
few to several dozen.
-The nuclei are often lobulated and located at the periphery of the cell, giving
it a distinctive appearance.
3. Mitotic Ability:
-Mature megakaryocytes, also known as polyploid megakaryocytes, undergo
endomitosis, a process where the cell replicates its DNA without subsequent
cell division.
-This results in a cell with multiple sets of chromosomes and contributes to the
formation of a large, multinucleated cell.
4. Nucleoli:
metabolic activity.
5. Cytoplasm:
metabolic activity.
-The cytoplasm of megakaryocytes is abundant
Megakaryocytes are located next to sinusoids, into
which they protrude their cytoplasmic processes. These
cytoplasmic processes fragment along complex, narrow
invaginations of the plasmalemma, known as demarcation
channels, into clusters of proplatelets.
B-THROMBOPOIESIS
Electron micrograph of a megakaryocyte
displaying segmentation in the formation of
platelets. Although this cell possesses a single
nucleus, it is lobulated, which gives the
appearance of
the cell possessing several nuclei (×3166).

31
2-Megakaryocyte B-THROMBOPOIESIS

32
2-Megakaryocyte B-THROMBOPOIESIS
Photomicrograph of bone marrow section
stained with H&E shows active
hemopoietic centers in a close proximity to
bone marrow sinusoids.

33
3-Proplatlets
1.Size and Shape:
-Proplatelets are elongated, filamentous structures resembling
a beaded necklace, with swellings along their length that will
eventually give rise to individual platelets.
-They vary in size but are typically much smaller than the
parent megakaryocyte.
-As megakaryocytes extend proplatelets into the bloodstream,
platelets are released from the tips of these extensions.
-Various factors, including shear forces in the bloodstream and
interactions with endothelial cells, contribute to the regulation
of proplatelet formation and platelet release.
2. Nucleus:
-Proplatelets are formed by the cytoplasmic extensions of
mature megakaryocytes, and they lack a distinct nucleus
themselves.
3. Mitotic Ability:
-Proplatelets are not capable of mitosis as they represent a
specialized stage in the differentiation of megakaryocytes.
4. Cytoplasm:
-The cytoplasm of proplatelets contains the cellular
components necessary for platelet function, including granules
and other organelles.
-The unique beaded structure along the proplatelets allows for
the distribution of these components in a controlled manner.
-Under electron microscopy, proplatelets reveal their
filamentous structure, often resembling a string of beads.
-Granules and other cytoplasmic components are visible along
the length of the proplatelets, and the ends exhibit a bulbous
structure where platelets will eventually be released.
The megakaryocyte cytoplasm is converted into a mass of proplatelets, which are released
from the cell. The nucleus is eventually extruded from the mass of proplatelets, and
individual platelets are released from proplatelet ends.
https://www.jci.org/articles/view/26891
https://www.science.org/doi/10.1126/science.1148946
B-THROMBOPOIESIS

34
3-Proplatlets
Representative images of in situ bone marrow proplatelets; several elongated
proplatelets (arrows) observed in a sinusoid vessel by scanning electron microscopy
(SEM). Inset, magnification showing a bulbous proplatelets end. Note the various
proplatelets shaft widths.
https://www.haematologica.org/article/view/9731
B-THROMBOPOIESIS

35
Overview of proplatelet formation. The assembly of platelets
from megakaryocytes involves an elaborate dance that
converts the cytoplasm into 100- to 500-μm-long branched
proplatelets on which the individual platelets develop. The
proplatelet and platelet formation process generally
commences from a single site on the megakaryocyte where 1
or more broad pseudopodia form. Over a period of 4–10
hours, the pseudopodial processes continue to elongate and
become tapered into proplatelets with an average diameter of
2–4 μm. Proplatelets are randomly decorated with multiple
bulges or swellings, each similar in size to a platelet, which
gives them the appearance of beads connected by thin
cytoplasmic strings (look at the opposite figure). The
generation of additional proplatelets continues at or near the
original site of proplatelet formation and spreads in a wavelike
fashion throughout the remainder of the cell until the
megakaryocyte cytoplasm is entirely transformed into an
extensive and complex network of interconnected proplatelets.
The multilobed nucleus of the megakaryocyte cell body is
compressed into a central mass with little cytoplasm and is
eventually extruded and degraded. Platelet-sized swellings
also develop at the proplatelet ends and are the primary sites
of platelet assembly and release, as opposed to the swellings
along the length of the proplatelet shaft (Figure 1). The
precise events involved in platelet release from proplatelet
ends have not been identified.
Differential interference contrast image of proplatelets
on a mouse megakaryocyte in vitro. Some of the
hallmark features of proplatelets, including the tip,
swellings, shafts, and a branch point, are indicated.
Scale bar, 5 μm.
3-Proplatlets B-THROMBOPOIESIS

36
4-Platelets
1. Size and Shape:
-Platelets are tiny, discoid cell fragments
with an average diameter ranging from 2 to
3 micrometers.
-They possess a flattened, discoid shape,
allowing them to navigate through blood
vessels.
2. Nucleus:
-Platelets do not have a nucleus. The
absence of a nucleus allows for increased
flexibility and better functionality in their role
during blood clotting.
3. Mitotic Ability:
-Platelets are incapable of mitosis or cell
division. They are derived from mature
megakaryocytes through a unique process
of cytoplasmic fragmentation.
4. Cytoplasm:
-The cytoplasm of platelets contains various
organelles, including dense granules and
alpha-granules, which store bioactive
molecules and proteins involved in blood
clotting.
-Under electron microscopy, platelets reveal
a granular cytoplasm, with a distinctive open
canalicular system that aids in the exchange
of substances with the surrounding plasma.
B-THROMBOPOIESIS

C-GRANULOPOIESIS

Granulocyte,erythrocyte,monocyte, Megakaryocyte
(CFU-GEMM)
Granulocyte-Monocyte progenitor (GMP) or (CFU-GM)
CFU-G/CFU-Eo/CFU-Ba
myeloblast
promyelocyte
Neutrophilic/eosinophilic/basophilic myelocyte
Neutrophilic/eosinophilic/basophilic metamyelocyte
Neutrophil/eosinophil/basophil
38
C-Granulopoiesis
Granulocytopoiesis, the formation of the granulocytes neutrophils, eosinophils, and
basophils, and mast cells is under the influence of several cytokines, including stem cell
factor, G-CSF and GM-CSF, PU.1 transcription factor, as well as IL-3, IL-5, IL-6, IL-8,
and TNF-α.
C-GRANULOPOIESIS
-if IL-5 is present, it drives the differentiation toward the formation of eosinophils.
In the absence of IL-5, basophils form.
-Mast cells also arise from myeloblasts but require stem cell factor for their differentiation

39
1-Myeloblast
The myeloblast is the earliest microscopically recognizable precursor cell in the
bone marrow.
1.Size and Shape:
-Myeloblasts are typically ranging in size from 12 to 14 micrometers in diameter.
-They exhibit a round or oval shape with a high nuclear-to-cytoplasmic ratio.
2. Nucleus:
-Myeloblasts have a single, large, round nucleus with fine chromatin.
-The nucleus is centrally located within the cell.
3. Mitotic Ability:
-Myeloblasts are highly mitotic and actively undergo cell division.
4. Nucleoli:
- Myeloblasts may have three to five prominent nucleoli within the nucleus.
-Nucleoli are involved in ribosomal RNA synthesis, reflecting the cell's high
metabolic activity.
5. Cytoplasm:
-The small amount of agranular cytoplasm stains intensely basophilic.
-It contains Developing organelles, including rough endoplasmic reticulum (rER)
and Golgi apparatus, are present in the cytoplasm, indicative of the cell's active
protein synthesis.
-A Golgi area is often seen where the cytoplasm is unstained.
-no granules are present
C-GRANULOPOIESIS

40
2-Promyelocyte
1.Size and Shape:
-Promyelocytes are moderately-sized cells, typically ranging from 14 to 18
micrometers in diameter.
-They exhibit a round or oval shape with a nucleus that is still relatively large.
2. Nucleus:
-Promyelocytes have a large, round nucleus with fine chromatin.
-The nucleus may contain one or more nucleoli, indicative of the cell's active
metabolic state.
3. Mitotic Ability:
-Promyelocytes maintain some mitotic activity, allowing for further proliferation
and differentiation into more mature granulocytic cells.
-This stage represents a transitional phase in which the cell is preparing for
specialization.
4. Nucleoli:
-Promyelocytes may have one or more nucleoli within the nucleus.
-Nucleoli are involved in ribosomal RNA synthesis, supporting the cell's protein
synthesis machinery.
5. Cytoplasm:
-The cytoplasm of promyelocytes is less basophilic compared to earlier stage
-Promyelocytes exhibit the formation of primary or azurophilic granules, which
are the initial granules in the development of granulocytes.
-Promyelocytes do not exhibit subtypes. Recognition of the neutrophil, eosinophil,
and basophil lines is possible only in the next stage.
C-GRANULOPOIESIS

41
3-Myelocyte
1.Size and Shape:
•Myelocytes are typically ranging from 10 to 12 micrometers in diameter.
•They exhibit a round or slightly indented shape.
2. Nucleus:
-Myelocytes have a rounded or slightly indented nucleus. It acquires a distinct indentation during subsequent divisions.
-The nucleus is still present in the cell but begins to show signs of condensation.
3. Mitotic Ability:
-Myelocytes have reduced mitotic activity compared to earlier precursor cells.
-The decrease in mitotic activity signifies a transitional phase toward further specialization.
4. Nucleoli:
-Myelocytes generally lack nucleoli
5. Cytoplasm:
-Specific granules in the cytoplasm become more apparent, indicating the cell's commitment to a specific granulocytic lineage.
C-GRANULOPOIESIS

42
4-Metamyelocyte
1.Size and Shape:
-Metayelocytes are typically ranging from 10 to 12 micrometers
in diameter.
2. Nucleus:
- They exhibit an indented or kidney-shaped nucleus,
distinguishing them from earlier stages, with ongoing nuclear
condensation.
3. Mitotic Ability:
-Metamyelocytes have no mitotic ability. They represent a post-
mitotic stage in granulocyte development. The reduction in
mitotic activity indicates the commitment to the final stages of
differentiation.
4. Nucleoli:
-Metamyelocytes generally lack nucleoli, indicating a further
reduction in ribosomal RNA synthesis activity compared to
earlier stages.
5. Cytoplasm:
- A few hundred granules are present in the cytoplasm of each
metamyelocyte, and the specific granules of each variety
outnumber the azurophilic granules.
- Organelle population is reduced
theoretically, the metamyelocyte stage in granulopoiesis is
followed
by the band stage and then the segmented stage. Although
these stages are obvious in the neutrophil line, they are rarely,
if ever, observed in the eosinophil and basophil lines in which
the next easily recognized stages of development are the
mature eosinophil and mature basophil, respectively.
C-GRANULOPOIESIS

43
5-Band (stab) cell
Band cells, also known as stab cells, are a stage in the maturation of granulocytes,
specifically neutrophils. Here are key characteristics associated with band/stab
cells:
1.Size and Shape:
- Band cells are typically ranging from 9 to 12 micrometers in diameter.
2. Nucleus:
- They are characterized by a distinctive elongated and of nearly
uniform width; thus giving them horseshoe or band-like appearance., which sets
them apart from earlier stages in granulopoiesis.
- It may exhibit condensation, indicating ongoing nuclear maturation.
-in further maturation; Nuclear constrictions then develop to show nuclear
lobulation
3. Mitotic Ability:
- Band/stab cells are post-mitotic, meaning they have limited or no mitotic ability.
-They represent a stage of granulocyte maturation that has progressed beyond the
mitotic phases.
4. Nucleoli:
-Band/stab cells generally lack nucleoli, indicating a further reduction in the cell's
metabolic and synthetic activities compared to earlier stages.
5. Cytoplasm:
- Band/stab cells contain specific granules that are more developed compared to
earlier stages.
-These granules contain enzymes and proteins involved in the immune response
and antimicrobial activities.
-Organelle population is reduced
Although the percentage of band cells in the circulation
is almost always low (0% to 3%), it may increase in acute or
chronic inflammation and infection.
.
C-GRANULOPOIESIS

44
6-Mature cells C-GRANULOPOIESIS
Electron micrograph of a human mature
neutrophil. The nucleus shows the typical multilobed
confi guration with the
heterochromatin at the periphery and the euchromatin
more centrally located. A small Golgi apparatus (G) is
present; other organelles are sparse. The
punctate appearance of the cytoplasm adjacent to the
convex aspect of the nuclear profi le is caused by
glycogen particles. Adjacent to the concave
aspect of the nuclear profi le are numerous granules.
Specifi c granules appear less dense and more
rounded than azurophilic granules. The latter are
fewer in number and are extremely electron dense.
Electron micrograph of a human eosinophil.
The nucleus is bilobed, but the connecting
segment is not within the plane
of section. The granules are of moderate size,
compared with those of the basophil, and show a
crystalline body (Cr) within the less electron-
dense
matrix of the granule. M, mitochondria
Electron micrograph of a human
basophil. The nucleus appears as three
separate bodies; the connecting strands
are
not in the plane of section. The basophil
granules (B) are very large and irregularly
shaped. Some granules reveal myelin fi
gures (MF). M, mitochondria.

45
Newly formed neutrophils leave the hemopoietic
cords by piercing the endothelial cells lining the sinusoids
rather than by migrating between them.
C-GRANULOPOIESIS

D-MONOPOIESIS

Granulocyte,erythrocyte,monocyte, Megakaryocyte (CFU-
GEMM)
Granulocyte-Monocyte progenitor (GMP) or (CFU-GM)
Monocyte progenitor (CFU-M) or Monoblast
promonocyte
Monocyte
Macrophage, monocyte-derived dendritic cells, osteoclast
and microglia
48
D-Monopoiesis D-MONOPOIESIS

49
1-Monoblast
Monoblasts are precursor cells in the process of monocytopoiesis,
representing an early stage in the development of monocytes. Here are
key characteristics associated with monoblasts:
1.Size and Shape:
-Monoblasts are relatively large cells with a diameter ranging from 14 to 20
micrometers.
-They typically exhibit a round or oval shape.
2. Nucleus:
-Monoblasts have a single, large, and centrally located nucleus.
-The nucleus is typically round or oval in shape and contains fine chromatin.
3. Mitotic Ability:
-Monoblasts possess the ability to undergo mitosis, allowing for cell division
and the generation of additional precursor cells in the monocyte lineage.
4. Nucleoli:
-Monoblasts may have one or more prominent nucleoli within the nucleus.
metabolic activity.
5. Cytoplasm:
-The cytoplasm of monoblasts is abundant and basophilic, meaning it stains
blue-purple with basic dyes.
-It contains developing organelles, including rough endoplasmic reticulum
(rER) and Golgi apparatus, indicative of the active protein synthesis
characteristic of precursor cells.
D-MONOPOIESIS
monoblasts in blood film are observed in
monoblastic and myelomonocytic leukemias.

50
2-Promonocyte
Promonocytes are intermediate cells in the process of monocytopoiesis, representing a stage between
monoblasts and mature monocytes. The transformation of MoPs to monocytes takes about 55 hours,
Here are key characteristics associated with promonocytes:
1.Size and Shape:
-Promonocytes are similar to the monoblast, with a diameter ranging from 14
to 20 micrometers.
-They exhibit a round or slightly indented shape.
2. Nucleus:
-Promonocytes typically have a single, large, and eccentrically located
nucleus.
-The nucleus may exhibit irregular contours (indented) and a finer chromatin
pattern compared to earlier precursor cells
3. Mitotic Ability:
-Promonocytes retain the ability to undergo mitosis, allowing for further
proliferation and differentiation into mature monocytes.
-The mitotic activity contributes to the expansion of the monocyte population.
4. Nucleoli:
-The nucleus of promonocytes may contain one or more nucleoli, although
they are generally less prominent than in earlier precursor cells.
-Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's
ongoing metabolic activity.
5. Cytoplasm:
-The cytoplasm of promonocytes is abundant and exhibits a slight basophilia.
-Developing organelles, including rough endoplasmic reticulum (rER) and
Golgi apparatus, are present in the cytoplasm, supporting the cell's protein
synthesis activities.
D-MONOPOIESIS

51
3-Monocyte
Monocytes representing the final stage of differentiation in the monocytopoiesis process.
Here are key characteristics associated with monocytes:
1.Size and Shape:
-Monocytes are relatively large cells with a diameter ranging from 12
to 20 micrometers.
2. Nucleus:
-Monocytes have a single, large, and kidney-shaped nucleus that may
exhibit a folded or lobulated appearance.
-The nucleus is often eccentrically located within the cell.
3. Mitotic Ability:
-Fully mature monocytes have limited mitotic ability. They typically
circulate in the bloodstream in a non-dividing state.
-In response to certain stimuli, monocytes can migrate to tissues where
they may undergo further differentiation into macrophages, monocyte-
derived dendritic cells, osteoclasts and microglia.
4. Nucleoli:
-Monocytes generally have a non-prominent nucleolus within the
nucleus.
5. Cytoplasm:
-The cytoplasm of monocytes is abundant and typically agranular and
contains various organelles such as lysosomes (azurophilic granules)
and endoplasmic reticulum.
-The cytoplasm may also display vacuoles, reflecting the cell's
phagocytic activity and ability to engulf foreign particles.
D-MONOPOIESIS

E-LYMPHPOIESIS

54
E-lymphopoiesis E-LYMPHOPOIESIS
1. Hematopoietic Stem Cells (HPSCs):
2. Common Lymphoid Progenitor (CLP) or (CFU-Ly):
The differentiation of CFU-Ly to CFU-LyB and CFU-LyT requires he expression of zinc finger proteins,
namely the Ikaros family of transcription factors as well as the expression of a moderate level of PU.1
transcription factor.
3. B and T Cell Commitment and Maturation:
B-cells: CFU-LyB in bone marrow divides several times, giving rise to immunocompetent B
lymphocytes expressing specific surface markers, including antibodies. - B cells undergo rearrangement
of their immunoglobulin genes, leading to the expression of unique B cell receptors (BCRs). Mature B
cells with functional BCRs are released into the bloodstream.
T-cells: CFU-LyT cells undergo mitosis, forming immunoincompetent T cells, which travel to the cortex
of the thymus, where they proliferate, mature, and begin to express cell surface markers. As these surface
markers appear on the T-cell plasmalemma the cells become immunocompetent T lymphocytes. Most of
these newly formed T cells are destroyed in the thymus and are phagocytosed by resident macrophages.
The process of T cell maturation is partially controlled by IL-7 and GATA3 transcription factor.
NKC: NK cells also migrate to a yet unknown region of the bone marrow where they will become
immunocompetent. The process of NK cell maturation is partially controlled by IL-12 and IL-15.
Migration and Circulation:
- Mature lymphocytes, including T cells, B cells, and NK cells, leave their sites of maturation (thymus
for T cells, bone marrow for B cells and NK cells) and enter the bloodstream.
- They circulate throughout the body, patrolling lymphoid tissues and organs.

55
E-lymphopoiesis E-LYMPHOPOIESIS

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