Haematopoiesis generates a variety of distinct blood cell types from a common stem cell. Secreted signalling molecules called cytokines modulate the survival, proliferation and differentiation of all the blood cell lineages, mediated by defined sets of transcription factors. Haematopoiesis is also influenced by external cues such as oxygen concentration. Haematopoiesis is an ongoing process continuing throughout lifetime, although the location of stem cells, and the specific cell types derived from them, changes during embryonic, foetal and early postnatal development. In the adult, haematopoiesis occurs primarily in the bone marrow, in association with a supportive niche. Haematopoietic stem cells are derived from cells bipotential for blood and endothelial cells, or directly from specialised endothelium. Blood lineages have a hierarchical relationship, but there is some flexibility among progenitors for deriving specific fates. Defects in haematopoiesis result in common and serious human diseases including anaemia and leukaemia.

Key Concepts

  • Haematopoiesis is the process of forming blood cells, which occurs during embryogenesis and throughout life.
  • Defects in haematopoiesis can result in some of the most common and serious human diseases, including anaemia and leukaemia.
  • Blood consists of many different kinds of cells with a diverse range of functions, controlling gaseous exchange and clotting and comprising the immune system.
  • All blood cells are derived from a common progenitor, the haematopoietic stem cell.
  • The sites where haematopoiesis occurs change during embryonic development, but in adult mammals, the bone marrow is the major site of haematopoiesis.
  • Haematopoietic stem cells in the bone marrow reside in a specialised microenvironment known as the haematopoietic stem cell niche, composed of osteoblasts, mesenchymal cells and sinusoidal vessels.
  • Growth factors called cytokines control the survival, self‐renewal and differentiation of haematopoietic stem cells and their progeny.
  • Blood cells have a close developmental relationship with endothelial cells, and haematopoietic stem cells appear to derive from ‘haemogenic endothelium’.
  • Haematopoiesis is also regulated by external factors. For example, hypoxia results in a compensatory increase in the number of erythrocytes.
  • Much effort is currently focused on generating and manipulating haematopoietic stem cells in vitro, to develop new regenerative therapies.

Keywords: blood; stem cell; cell lineage; cytokines; niche; haemoglobin

Figure 1. Schematic illustrating a generally accepted hierarchical relationship among haematopoietic stem cells and adult‐stage blood cells. The long‐term reconstituting haematopoietic stem cell (LTRC) maintains itself, and gives rise to myeloid and lymphoid cells through several intermediate progenitor stages. Short‐term reconstituting haematopoietic stem cells (STRC) have limited self‐renewal capacity and give rise to multipotent progenitors (MPPs) that lack self‐renewal capacity but have strong proliferative capacity. Common myeloid progenitors (CMPs) are the earliest committed myeloid progenitor and eventually differentiate into mature cells through the intermediate stages of megakaryocyte‐erythroid progenitors (MEPs) and granulocyte‐monocyte progenitors (GMPs). Common lymphoid progenitors (CLPs) have the capacity to differentiate into a B cell, NK cell or T cell, but whether they represent a physiological T‐cell progenitor is controversial. It has been hypothesised that early thymic progenitors (ETPs) bypass the stage of CLPs, and are the physiological T‐cell progenitors, although further studies are needed to clarify the pathways (indicated by question marks).
Figure 2. A schematised view of the haematopoietic niche. Haematopoietic stem cells (HSCs) in the bone marrow cavity lay in perivascular niches very close to blood vessels, where endothelial cells (ECs) and mesenchymal stromal cells (MSCs) provide signals for HSC maintenance. Osteoblasts in the endosteal niche promote the maintenance and most likely differentiation of haematopoietic stem and progenitor (HSP) cells.
Figure 3. Organisation of the human β‐like globin genes on chromosome 11. The black line represents the deoxyribonucleic acid of the chromosome and the boxes represent individual globin genes (the illustration is not drawn to scale). Each gene is transcribed in the same direction (arrow) and in the same developmental order as arranged on the chromosome. Erythroid cells that develop in a different location express distinct globin genes. Although not shown here, each gene has its own regulatory elements (promoters and enhancers) and the entire locus is regulated in addition by a sequence located far upstream, distal to the ϵ gene (the locus control region or LCR). The pseudo‐gene is not expressed; it is thought to be an evolutionary remnant. ‘Switching’ occurs for the embryonic and adult α‐like globin genes on chromosome 16, although the mechanism may differ.
Figure 4. Potential plasticity of haematopoietic progenitors. As schematised here, mature haematopoietic cells or progenitors may be diverted from their normal developmental potential and redirected to new cell fates by ectopic cytokine signalling or forced expression of regulatory genes. Mature B cells and T‐cell progenitors (ETPs) can be trans‐differentiated into macrophages by forced expression of C/EBPα. Downregulation of Pax5 (Pax5‐) results in dedifferentiation of mature B cells into uncommitted progenitors that can be differentiated to mature T cells. Forced expression of the transcription factors Oct3/4, Sox2, Klf4 and cMyc can induce dedifferentiation of B cells (coupled with downregulation of Pax5) and T cells into ESC‐like cells known as induced pluripotent stem cells (iPSCs). B‐cell and myeloid cell progenitors can be reprogrammed into transplantable HSC‐like cells by induction of six transcription factors: Run1t1, Hlf, Lmo2, Prdm5, Pbx1 and Zfp37.


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Further Reading

Kondo M (2009) Hematopoietic Stem Cell Biology (Stem Cell Biology and Regenerative Medicine). New York: Humana Press.

Metcalf D and Moore MAS (1971) Haemopoietic Cells. Amsterdam: North‐Holland.

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Thompson AW and Lotze MT (2003) The Cytokine Handbook, 4th edn. San Diego: Academic Press.

Zon L (2001) Hematopoiesis: A Developmental Approach. Oxford: University Press.

For Images

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American Society of Hematology, Image Bank [http://imagebank.hematology.org/]

National Institutes of Health, Stem Cell Information Page, Hematopoietic Stem Cells [http://stemcells.nih.gov/info/Regenerative_Medicine/Pages/2006Chapter2.aspx]

Slideshare [http://www.slideshare.net/balsan/normal‐hematopoiesis]

University of Nebraska at Omaha, Blood Cell Histology [http://www.unomaha.edu/hpa/blood.html]

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Kumar, Ritu, and Evans, Todd(Jun 2015) Haematopoiesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000518.pub4]