Haematopoiesis

Ritu Kumar, Weill Cornell Medical College, New York, USA
Todd Evans, Weill Cornell Medical College, New York, USA

Published online: June 2010

DOI: 10.1002/9780470015902.a0000518.pub3

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, fetal 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, clotting and comprising the immune system.
  • All blood cells are derived from a common progenitor, the haematopoietic stem cell.
  • The site where haematopoiesis occurs changes 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, comprised of osteoblasts 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 ‘hemogenic endothelium’.
  • Mature blood cells can be prompted to dedifferentiate or trans-differentiate into other cell types, although this may normally be a rare event.
  • Haematopoiesis is also regulated by external factors. For example, hypoxia results in a compensatory increase in the number of erythrocytes.

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

Figure 1. Schematic illustrating potential 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 (MPP) that lack self-renewal capacity. Common myeloid progenitors (CPM) are the earliest committed myeloid progenitor and eventually differentiate into mature cells through the intermediate stages of megakaryocyte-erythroid (MEP) and granulocyte-monocyte progenitors (GMP). Common lymphoid progenitors (CLP) 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 (ETP) bypass the stage of CLP, and are the physiological T-cell progenitors, although further studies are needed to clarify the pathways (indicated by?).
Figure 2. A schematised view of the haematopoietic niche. Haematopoietic stem cells (HSCs) in the bone marrow cavity lie in close association with osteoblasts lining the endosteum. Osteoblasts are thought to serve as niche (stromal) cells to maintain quiescence and prevent differentiation of associated HSCs. HSCs in bone marrow can also be found very close to blood vessels in perivascular niches (sinusoidal vessels). These perivascular spaces may provide a niche for HSCs, a transitory site for maturation or an exit point for circulation.
Figure 3. Organisation of the human -like globin genes on chromosome 11. The black line represents the DNA 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 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 -like globin genes on chromosome 16, although the mechanism may differ.
Figure 4. Potential plasticity of the 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- and T-cell progenitors (ETP) can be trans-differentiated into macrophages by forced expression of C/EBP. 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 c-Myc, coupled with downregulation of Pax5, can induce dedifferentiation of B cells into embryonic stem-like cells known as induced pluripotent stem (iPS) cells.
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    book Levitt D and Mertesmann R (1995) Hematopoietic Stem Cells. New York: Marcel Dekker, Inc.
    book Metcalf D and Moore MAS (1971) Haemopoietic Cells. Amsterdam: North-Holland.
    book Nathan DG and Orkin SH (1998) Nathan and Oski's Hematology of Infancy and Childhood, 5th edn. Philadelphia: WB Saunders.
    book Thompson A (1994) The Cytokine Handbook, 2nd edn. San Diego: Academic Press.
    book Zon L (2001) Hematopoiesis: A Developmental Approach. Oxford: University Press.
 Web Links
    ePath American Society of Hematology, Image Bank [http://ashimagebank.hematologylibrary.org/collections/]
    ePath National Institutes of Health, Stem Cell Information Page, Hematopoietic Stem Cells [http://stemcells.nih.gov/info/scireport/chapter5]
    ePath University of Nebraska at Omaha, Blood Cell Histology [http://www.unomaha.edu/hpa/blood.html]

Related Sub-Topics:

Cytokines | Cells of the Immune System
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Article Title: Haematopoiesis
 
How to Cite close
Kumar, Ritu, and Evans, Todd(Jun 2010) Haematopoiesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000518.pub3]