Hematopoiesis is the formation of blood cells from hematopoietic stem cells located in bone marrow. There are three main lineages - erythroid cells (red blood cells), lymphocytes (white blood cells involved in immunity), and myelocytes (other white blood cells). Hematopoietic stem cells self-renew and can differentiate into various mature blood cell types. Growth factors and cytokines regulate the proliferation, differentiation, and maturation of blood cell lineages, while transcription factors determine the specific lineages that cells develop into.

1. Haematopoiesis 1
Haematopoiesis
Haematopoiesis (from Ancient Greek:
αἷμα, "blood"; ποιεῖν "to make") (or
hematopoiesis in the United States;
sometimes also haemopoiesis or
hemopoiesis) is the formation of blood
cellular components. All cellular blood
components are derived from
haematopoietic stem cells. In a healthy
adult person, approximately 1011–1012
new blood cells are produced daily in
order to maintain steady state levels in
the peripheral circulation.[1] [2]
Hematopoietic stem cells Simple diagram that shows the development of different blood cells from haematopoietic
stem cell to mature cells
(HSCs)
Hematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to
give rise to all of the different mature blood cell types. HSCs are self renewing: when they proliferate, at least some
of their daughter cells remain as HSCs, so the pool of stem cells does not become depleted. The other daughters of
HSCs (myeloid and lymphoid progenitor cells), however can each commit to any of the alternative differentiation
pathways that lead to the production of one or more specific types of blood cells, but cannot self-renew. This is one
of the vital processes in the body.
Lineages
All blood cells are divided into three
lineages.
• Erythroid cells are the oxygen
carrying red blood cells. Both
reticulocytes and erythrocytes are
functional and are released into the
blood. In fact, a reticulocyte count
estimates the rate of erythropoiesis.
• Lymphocytes are the cornerstone of
the adaptive immune system. They
are derived from common lymphoid
progenitors. The lymphoid lineage
is primarily composed of T-cells
and B-cells (types of white blood Comprehensive diagram that shows the development of different blood cells from
haematopoietic stem cell to mature cells
cells). This is lymphopoiesis.
• Myelocytes, which include
granulocytes, megakaryocytes and macrophages and are derived from common myeloid progenitors, are involved
in such diverse roles as innate immunity, adaptive immunity, and blood clotting. This is myelopoiesis.
Granulopoiesis (or granulocytopoiesis) is haematopoiesis of granulocytes.

2. Haematopoiesis 2
Megakaryocytopoiesis is haematopoiesis of megakaryocytes.
Locations
In developing embryos, blood formation occurs in aggregates of blood cells in the yolk sac, called blood islands. As
development progresses, blood formation occurs in the spleen, liver and lymph nodes. When bone marrow develops,
it eventually assumes the task of forming most of the blood cells for the entire organism. However, maturation,
activation, and some proliferation of lymphoid cells occurs in secondary lymphoid organs (spleen, thymus, and
lymph nodes). In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In
adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum.
Extramedullary
In some cases, the liver, thymus, and spleen may resume their haematopoietic function, if necessary. This is called
extramedullary haematopoiesis. It may cause these organs to increase in size substantially. During fetal
development, since bones and thus the bone marrow, develop later, the liver functions as the main haematopoetic
organ. Therefore, the liver is enlarged during development.
Other vertebrates
In some vertebrates, haematopoiesis can occur wherever there is a loose stroma of connective tissue and slow blood
supply, such as the gut, spleen, kidney or ovaries.
Maturation
As a stem cell matures it undergoes changes in gene expression that limit the cell types that it can become and moves
it closer to a specific cell type. These changes can often be tracked by monitoring the presence of proteins on the
surface of the cell. Each successive change moves the cell closer to the final cell type and further limits its potential
to become a different cell type.
Determination
Cell determination appears to be dictated by the location of differentiation. For instance, the thymus provides an
ideal environment for thymocytes to differentiate into a variety of different functional T cells. For the stem cells and
other undifferentiated blood cells in the bone marrow, the determination is generally explained by the determinism
theory of haematopoiesis, saying that colony stimulating factors and other factors of the haematopoietic
microenvironment determine the cells to follow a certain path of cell differentiation. This is the classical way of
describing haematopoiesis. In fact, however, it is not really true. The ability of the bone marrow to regulate the
quantity of different cell types to be produced is more accurately explained by a stochastic theory: Undifferentiated
blood cells are determined to specific cell types by randomness. The haematopoietic microenvironment prevails
upon some of the cells to survive and some, on the other hand, to perform apoptosis and die. By regulating this
balance between different cell types, the bone marrow can alter the quantity of different cells to ultimately be
produced.

3. Haematopoiesis 3
Haematopoietic growth factors
Red and white blood cell production is
regulated with great precision in
healthy humans, and the production of
granulocytes is rapidly increased
during infection. The proliferation and
self-renewal of these cells depend on
stem cell factor (SCF). Glycoprotein
growth factors regulate the
proliferation and maturation of the
cells that enter the blood from the
marrow, and cause cells in one or more
committed cell lines to proliferate and
mature. Three more factors that
stimulate the production of committed
stem cells are called
colony-stimulating factors (CSFs) and
include granulocyte-macrophage CSF
(GM-CSF), granulocyte CSF (G-CSF)
and macrophage CSF (M-CSF). These
Diagram including some of the important cytokines that determine which type of blood
stimulate much granulocyte formation [3]
cell will be created. SCF= Stem Cell Factor Tpo= Thrombopoietin IL= Interleukin
and are active on either progenitor GM-CSF= Granulocyte Macrophage-colony stimulating factor Epo= Erythropoietin
cells or end product cells. M-CSF= Macrophage-colony stimulating factor G-CSF= Granulocyte-colony stimulating
factor SDF-1= Stromal cell-derived factor-1 FLT-3 ligand= FMS-like tyrosine kinase 3
Erythropoietin is required for a ligand TNF-a = Tumour necrosis factor-alpha TGFβ = Transforming growth factor beta
[4]
myeloid progenitor cell to become an
erythrocyte.[3] On the other hand,
thrombopoietin makes myeloid progenitor cells differentiate to megakaryocytes (thrombocyte-forming cells).[3]
Examples of cytokines and the blood cells they give rise to, is shown in the picture to the right.
Transcription factors
Growth factors initiate signal transduction pathways, altering transcription factors, that, in turn activate genes that
determine the differentiation of blood cells.
The early committed progenitors express low levels of transcription factors that may commit them to discrete cell
lineages. Which cell lineage is selected for differentiation may depend both on chance and on the external signals
received by progenitor cells. Several transcription factors have been isolated that regulate differentiation along the
major cell lineages. For instance, PU.1 commits cells to the myeloid lineage whereas GATA-1 has an essential role
in erythropoietic and megakaryocytic differentiation. The Ikaros, Aiolos and Helios transcription factors play a
major role in lymphoid development.[5]

4. Haematopoiesis 4
The myeloid-based model
For a decade now, the evidence is growing that HSC maturation follows a myeloid-based model instead of the
'classical' schoolbook dichotomy model. In the latter model, the HSC first generates a common myeloid-erythroid
progenitor (CMEP) and a common lymphoid progenitor (CLP). The CLP produces only T or B cells. The
myeloid-based model postulates that HSCs first diverge into the CMEP and a common myelo-lymphoid progenitor
(CMLP), which generates T and B cell progenitors through a bipotential myeloid-T progenitor and a myeloid-B
progenitor stage. The main difference is that in this new model, all erythroid, T and B lineage branches retain the
potential to generate myeloid cells (even after the segregation of T and B cell lineages). The model proposes the idea
of erythroid, T and B cells as specialized types of a prototypic myeloid HSC. Read more in Kawamoto et al. 2010.[6]
References
[1] Semester 4 medical lectures at Uppsala University 2008 by Leif Jansson
[2] Parslow,T G.;Stites, DP.; Terr, AI.; and Imboden JB.. Medical Immunology (1 ed.). ISBN 0838562787.
[3] Molecular cell biology. Lodish, Harvey F. 5. ed. : - New York : W. H. Freeman and Co., 2003, 973 s. b ill. ISBN 0-7167-4366-3
• For the growth factors also mentioned in previous version File:Hematopoiesis (human) cytokines.jpg: Molecular cell biology. Lodish,
Harvey F. 5. ed. : - New York : W. H. Freeman and Co., 2003, 973 s. b ill. ISBN 0-7167-4366-3
• The rest: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh:
Churchill Livingstone. ISBN 0-443-06911-5.
[5] Rebollo, A.; C. Schmitt (2003). "Ikaros, Aiolos and Helios: Transcription regulators and lymphoid malignancies". Immunology and Cell
Biology 81 (3): 171–175. doi:10.1046/j.1440-1711.2003.01159.x. PMID 12752680.
[6] Kawamoto, Wada, Katsura. A revised scheme for developmental pathways of haematopoietic cells: the myeloid-based model. International
Immunology 2010.
Further reading
• Godin, Isabelle & Cumano, Ana, ed (2006). Hematopoietic stem cell development (http://books.google.com/
books?id=tUsSmZwW_9MC). Springer. ISBN 9780306478727.
External links
• Granulopoiesis from tulane.edu (http://www.som.tulane.edu/classware/pathology/Krause/Blood/GP.html)

5. Article Sources and Contributors 5
Article Sources and Contributors
Haematopoiesis Source: http://en.wikipedia.org/w/index.php?oldid=433638250 Contributors: .:Ajvol:., A. Rad, AThing, Aamer86, AdultSwim, AlphaEta, AndrewJD, Antibody2000, Aquatech,
Arcadian, Ariostosilva, BarretBonden, BillC, Brazucs, Brim, Bryan Derksen, Buster79, Chrishmt0423, Conversion script, Cquan, Ctrlaltdelete200390, Dcirovic, Diberri, Dr. F.C. Turner,
DrGabriela, Enchanter, Essent, Giftlite, Glassneko, Jag123, Jer ome, Jeyradan, Jfdwolff, John254, Kaobear, Kauczuk, Kipmaster, Lateg, Lbiscuit1980, Leptictidium, Linzhoo2u, Liveste,
Markacohen, Mccready, Mdhellman, Mesoderm, Mikael Häggström, NewEnglandYankee, Nina, Nina Gerlach, Openlander, Pstragier, Qumsieh, R'n'B, Rakal87, Reedy, Rintrah,
Salwateama2008, Schmiteye, Snalwibma, Snek01, Snowmanradio, Some standardized rigour, Stephenb, TheAMmollusc, Tkkoski, 89 anonymous edits
Image Sources, Licenses and Contributors
File:Hematopoiesis simple.svg Source: http://en.wikipedia.org/w/index.php?title=File:Hematopoiesis_simple.svg License: GNU Free Documentation License Contributors: User:Mikael
Häggström
Image:Hematopoiesis (human) diagram.png Source: http://en.wikipedia.org/w/index.php?title=File:Hematopoiesis_(human)_diagram.png License: Creative Commons Attribution-ShareAlike
3.0 Unported Contributors: A. Rad
File:Hematopoietic growth factors.png Source: http://en.wikipedia.org/w/index.php?title=File:Hematopoietic_growth_factors.png License: GNU Free Documentation License Contributors:
User:Mikael Häggström and A. Rad
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