Description about origin of blood cells from bone marrow i.e. hematopisis and process of eryhtropoisis and its regulation,Leukopoisis includingformation of all type of WBC's, Useful for medical science,Post graduate ,and Undergraduate life science students.

1. HEMATOPOIESIS:
An Overview
Dr. Rashmi Morey
Pune District Education Association’s
Prof. Ramkrishna More College
Akurdi-Pune
moreyrashmi@gmail.com

2. Hematopoisis
Introduction:
• Hematopoiesis is the continuous, controlled process of restoration,
proliferation, differentiation, and maturation of all blood cells .
• It results in the formation, development, and specialization of all
functional blood cells that are released from the bone marrow into the
circulation.
• Before birth, hemopoiesis first occurs in the yolk sac of an embryo and
later in the liver, spleen, thymus, and lymph nodes of a fetus.
• Red bone marrow is the primary site of hemopoiesis in the last 3
months before birth, and continues as the source of blood cells after
birth and throughout life.

3. • Each type of blood cell is produced in different numbers in response to
changing body needs and different regulatory factors.
• As blood cells mature, they migrate through the thin walls of the
sinusoids to enter the bloodstream.
• On average, the marrow turns out an ounce of new blood containing
some 100 billion new cells each and every day .
• It occurs within the hematopoietic system, which includes organs and
tissues such as the bone marrow, liver, and spleen.
• Simply, hematopoiesis is the process through which the body
manufactures blood cells.
Hematopoisis….

4. Diagrammatic
representation
Age of
Human
Site of
hematopoiesis
Embryo Yolk Sac and
Liver
3rd-7th
Month
Spleen
4th & 5th
Month
Marrow Cavity
7th
Month
Marrow Cavity
Birth Marrow,
Spleen and
Liver if Needed
Upto
Maturity
Bone Marrow
Adult Bone marrow
of Skull, Ribs,
Sternum,
Vertebral
Column,
Femur
Diagrammatic
Representation
A. Rad and Mikael Häggström, M.D.

5. • Hematopoiesis begins during the first weeks of embryonic development.
• The process of hematopoiesis begins with an unspecialized stem cell. This stem
cell multiplies, and some of these new cells transform into precursor cells.
• These are cells that are destined to become a particular type of blood cell but
are not yet fully developed. However, these immature cells soon divide and
mature into blood components, such as red and white blood cells, or platelets.
• The rate of hematopoiesis depends on body’s need. The body continually
manufactures new blood cells to replace old ones.
Facts of hematopoiesis:

6. Origin of Blood Cell...
• Red bone marrow is a highly vascularized connective tissue located in
the microscopic spaces between trabeculae of spongy bone tissue
• It is present chiefly in bones of the axial skeleton, pectoral and pelvic
girdles, and the proximal epiphyses of the humerus and femur.
• About 0.05–0.1% of red bone marrow cells are called pluripotent stem
cells (PSC) or hemocytoblasts and are derived from mesenchyme
(tissue from which connective tissues develop).
• These cells have the capacity to develop into many different types of
cells.

7. • The various formed elements have different functions, but there are
similarities in their life histories. All arise from the same type of stem
cell, the hemocytoblast (cyte = cell, blast = bud), or pluripotent
hematopoietic stem cell
• These undifferentiated precursor cells reside in the red bone marrow.
The maturation pathways of the various formed elements differ,
however, and once a cell is committed to a specific blood cell pathway,
it cannot change.
• This commitment is signaled by the appearance of membrane surface
receptors that respond to specific hormones or growth factors, which in
turn “push” the cell toward further specialization.
Origin of Blood Cell ...

8. Erythropoiesis
• Erythrocyte production, or erythropoiesis begins when a hemocytoblast descendant
called a myeloid stem cell(MSC) is transformed into a proerythroblast
• Proerythroblasts, in turn, give rise to the early (basophilic) erythroblasts that produce
huge numbers of ribosomes
• During these first two phases, the cells divide many times. Hemoglobin is synthesized
and iron accumulates as the early erythroblast is transformed into a late erythroblast and
then a Normoblast
• The “color” of the cell cytoplasm changes as the blue-staining ribosomes become
masked by the pink color of hemoglobin.
• When a normoblast has accumulated almost all of its hemoglobin, it ejects most of its
organelles.
• Additionally, its nuclear functions end and its nucleus degenerates and is pinched off,
allowing the cell to collapse inward and eventually assume the biconcave shape.
• The result is the reticulocyte (essentially a young erythrocyte), so named because it still
contains a scant reticulum (network) of clumped ribosomes.

9. DiagrammaticRepresentation
chapter-17-erythropoiesis-genesis-of-red-blood-cells-diagram/

10. Regulation of Erythopoisis
• The stimulus for erythrocyte formation is provided by erythropoietin
(EPO), a glycoprotein hormone.
• Normally, a small amount of EPO circulates in the blood at all times
and sustains red blood cell production at a basal rate.
• The kidneys play the major role in EPO production, although the liver
produces some.
• When certain kidney cells become hypoxic (i.e., have inadequate
oxygen), oxygen-sensitive enzymes are unable to carry out their normal
functions of degrading an intracellular signaling molecule called
hypoxia-inducible factor (HIF).
• As HIF accumulates, it accelerates the synthesis and release of
erythropoietin.

11. Diagrammatic
Representation
http://www.mc3cb.com/pdf_ap_lectures/C19_2_hemopoiesis_eythropoiesis_leukopoiesis.

12. Leukopoiesis
• Leukopoiesis is the process of formation of leukocytes (white blood cells)
from stem cells in haematopoietic organs.
• leukocyte differentiation, starting with the hematopoietic stem cell(HSC), or
hemocytoblast, that gives rise to all of the formed elements in the blood.
• An early branching of the pathway divides the lymphoid stem cells, which
produce lymphocytes, from the myeloid stem cells, which give rise to all
other formed elements.
• In each granulocyte line, the committed cells, called myeloblasts (mie˘-
loblasts), accumulate lysosomes, becoming promyelocytes.
• The distinctive granules of each granulocyte type appear next in the
myelocyte stage and then cell division stops.
• In the subsequent stage, the nuclei arc, producing the band cell stage. Just
before granulocytes leave the marrow and enter the circulation, mature
neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes.

13. Diagrammatic
Representation
http://www.mc3cb.com/pdf_ap_lectures/C19_2_hemopoiesis_
eythropoiesis_leukopoiesis.

14. Neutrophils
• Under the stimulation of cytokines GM-CSF, G-CSF and IL-3 the CFU-GEMM differentiates into the CFU-GM,
the common precursor for both neutrophils and monocytes. This then further differentiates into CFU-G.
• Stages:
• Myeloblast
• Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.
• Promyelocyte
• During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.
• Neutrophilic myelocyte
• The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules
are now being formed.
• Neutrophilic metamyelocyte
• At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like
shape. Differentiation is much clearer from other granulocytes as the specific granules are in a far greater number
than the primary granules formed in the promyelocyte stage.
• Band cell
• Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
• Neutrophil
• Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus
gives rise to the name polymorphonuclear neutrophil.

15. Basophils
• Under the stimulation of GM-CSF and IL-3, the CFU-GEMM differentiates
into CFU-Ba.
• Stages:
• Myeloblast & Promyelocyte
• These stages are common to all granulocytes and no distinction can be made
between different cell lines.
• Basophilic myelocyte & metamyelocyte
• Specific granules start to appear in the myelocyte stage, and as the cell develops
into the metamyelocyte stage, mitosis ceases.
• Basophil
• Final nuclear shape is masked by the high density of cytoplasmic granules.

16. Eosinophils
• Under the stimulation of GM-CSF, IL-3 and IL-5 the CFU-GEMM differentiates
into the CFU-Eo.
• Stages:
• Myeloblast & Promyelocyte
• These stages are common to all granulocytes and no distinction can be made
between different cell lines.
• Eosinophilic myelocyte & metamyelocyte
• Specific granules start to appear in the myelocyte stage and once the cell has
reached the metamyelocyte stage it cannot undergo further mitosis.
• Eosinophil
• Mature cell has a bilobed nucleus. There are species specific variations in granule
size once stained.

17. Monocytes
• Monocytes develop from the same precursor as neutrophils - the CFU-GM. This then
differentiates into the CFU-M under the influence of GM-CSF, IL-3 and M-CSF.
• Stages:
• Monoblast
• This is the first stage after cell has differentiated into the CFU-M.
• Promonocyte
• Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly
dividing and the other slowly dividing, which acts as a reservoir.
• Monocyte
• Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped
nucleus with a slightly basophilic cytoplasm, which is often vacuolated.
• Macrophage
• Once the monocyte has entered tissue it differentiates into a macrophage.
• Dendritic cells
• These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature
dendritic cell. This then develops into the mature dendritic cell under stimulation of TNF-α.

18. Diagrammatic Representation
Origin-and-development-of-macrophages-and-neutrophils-a-
The-generation-of-macrophages-is_fig1_313671642

19. Lymphopoiesis
• Lymphocytes develop from the CFU-L's.
• Those destined to become T cells leave the bone marrow and migrate
to the thymus,
• and those destined to be B cells migrate to the spleen and gut-
associated lymphoid tissue (GALT) or proliferate directly from the bone
marrow.

20. B cell T cell
Differentiation
CFU-L
▼IL-7 & IL-11 ▼IL-7 & SCF
B lymphoid cell
progenitor
T lymphoid cell progenitor
▼IL-3 & IL-7 ▼IL-7 ▼IL-2, IL-12 & IL-18
▼IL-3, IL-6,
GM-CSF & SCF
Pre-B cell
Pre-T
cell
Pre-NK cell Pre-Dendritic cell
Maturation
site
Bone marrow,
spleen or GALT
Cloacal bursa
(birds)
Thymus
Mature
B cell
▼(Antigen stim.)
Plasma & Memory
cell
T Cell
Helper
Cytotoxic
Regulatory
NK cell Dendritic cell
Lymphopoiesis:
Lymphocytes develop
from the CFU-L's.
Those destined to
become T cells leave
the bone marrow and
migrate to
the thymus, and those
destined to be B
cells migrate to
the spleen and gut-
associated lymphoid
tissue (GALT) or
proliferate directly
from the bone
marrow. https://en.wikivet.net/Leukopoiesis

21. • Despite their similar appearances, the two types of agranulocytes have
very different lineages.
• Monocytes are derived from myeloid stem cells, and share a common
precursor with neutrophils that is not shared with the other
granulocytes.
• Cells following the monocyte line pass through the monoblast and
promonocyte stages before leaving the bone marrow and becoming
monocytes.
• Lymphocytes derive from the lymphoid stem cell and progress through
the lymphoblast and prolymphocyte stages.
• The prolymphocytes leave the bone marrow and travel to the lymphoid
tissues, where their further differentiation occurs.
Agranulopoiesis

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