Key Points
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Stem cells have two main properties — self-renewal and multipotentiality.
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It was shown recently that two independent generation events of haematopoietic stem cells (HSCs) occur in the extra-embryonic (yolk sac) and intra-embryonic compartments.
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These two types of precursor coexist in early vertebrate embryos. The precursors that originate in the yolk sac are not multipotent and have a limited self-renewal capacity. The other type of precursor, which originates in the intra-embryonic para-aortic region, has both features of HSCs. These observations indicate that self-renewal and multipotentiality cannot be dissociated.
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Extra-embryonic precursors give rise to specific subsets of mature erythromyeloid cells that have an accelerated differentiation rate compared with the intra-embryonic-derived progenitors. So, haematopoietic development relies on a dual contribution — first, from a fast then exhausted extra-embryonic precursor (the hare), and then from a slowly developing and long-lasting intra-embryonic HSC (the tortoise).
Abstract
Cellular and gene therapy are obvious approaches to correct rare genetic disorders and, in the future, degenerative conditions. Both methods rely on the ability to identify and genetically modify stem cells in vitro, and on the reproducibility of in vivo colonization by the manipulated cells. The basic processes that are involved in the generation of haematopoietic cells in the embryo have been described in the past ten years, as a result of interdisciplinary approaches. These efforts have led to the identification of two independently generated types of haematopoietic progenitor cell, which differ in their potential for self-renewal and differentiation. These two populations might become key tools to understand the properties of stem cells.
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Acknowledgements
I.G. and A.C. are supported by grants from the French Ministry of Research (ACI developmental biology), and I.G. is supported by a grant from the 'Association pour la Recherche sur le Cancer'. The 'Unité du Développement des Lyphocytes' is supported by the 'Ligue Nationale de la Recherche contre le Cancer' as a registered laboratory.
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DATABASES
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Glossary
- HAEMATOPOIESIS
-
The commitment and differentiation processes that lead from a haematopoietic stem cell to the production of mature cells of all lineages — erythrocytes, myeloid cells (macrophages, mast cells, neutrophils and eosinophils), B and T cells, and natural killer cells.
- HAEMATOPOIETIC STEM CELLS
-
Cells that have the ability to both generate all types of haematopoietic cell (multipotentiality) and replace themselves (self-renewal) throughout the lifetime of an individual. Whereas multipotentiality can be assessed in vitro and in vivo, self-renewal can be determined only by the in vivo detection of long-term reconstitution activity.
- PRIMITIVE/DEFINITIVE
-
This term refers to specific haematopoietic lineages that arise early or late during embryogenesis or to early/late phases of the haematopoietic process.
- SPECIFIC LINEAGES
-
Mature cells are qualified as 'primitive' when they have features that are present only in early embryos — for example, primitive erythrocytes synthesize a type of globin that is expressed only during ontogeny. Mature cells that have the same characteristics irrespective of whether they are present in embryos or adults are known as 'definitive'.
- WHOLE PROCESS OF HAEMATOPOIESIS
-
Primitive haematopoiesis refers to blood-cell production originating from the yolk sac. Definitive haematopoiesis is carried out in the fetal liver in the embryo, from haematopoietic stem cells that are generated initially in the splanchnopleura/aorta–gonad–mesonephros, and then in the bone marrow of adults.
- ERYTHROPOIESIS
-
The differentiation process leading from a committed erythroid precursor to the production of mature red blood cells (erythrocytes).
- AORTA–GONAD–MESONEPHROS
-
(AGM). The embryonic site at which definitive haematopoietic stem cells (HSCs) are produced. It comprises the aorta, and developing reproductive and excretory (mesonephros) systems. Within this haemogenic site, HSCs are concentrated in the aorta region.
- MONOCYTE
-
An intermediate cell type in the pathway leading from a myeloid precursor to a differentiated macrophage.
- PLOIDY
-
The DNA content of the nucleus, which is usually 2N. Megakaryocytes synthesize DNA without cytokinesis. In the adult, their ploidy is 16N.
- HAEMOGENIC SITE
-
The site at which de novo generation of haematopoietic cells occurs. Two haemogenic sites have been identified in the embryo — the yolk sac and an intra-embryonic site, the splanchnopleura/aorta–gonad–mesonephros region.
- SOMITE
-
Somites are the result of bilateral cell condensation in the dorsal body wall of vertebrate embryos. The somitic cells are founders of the skeletal muscle of the body wall, the back and the limbs, of the dermis, and of the vertebrae and ribs. Somite counting is a precise way to assess the developmental stage of a rapidly changing embryo, because an additional pair of somites are added about every two hours.
- HAEMANGIOBLAST
-
A presumptive cell type that can give rise to endothelial cells and haematopoietic cells. The existence of these bi-lineage precursors, still not proved formally, was inferred from the observation that in the early-embryo yolk sac, blood vessels and circulating cells arise from apparently homogeneous cell clusters.
- BLASTOMERE
-
A cell that results from the cleavage of the zygote.
- LONG-TERM RECONSTITUTION (LTR) ACTIVITY
-
The capacity of a haematopoietic precursor to reconstitute all lineages for more than six months (long term) when injected into an irradiated mouse. It reveals the self-renewal capacity of haematopoietic stem cells.
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Godin, I., Cumano, A. The hare and the tortoise: an embryonic haematopoietic race. Nat Rev Immunol 2, 593–604 (2002). https://doi.org/10.1038/nri857
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DOI: https://doi.org/10.1038/nri857
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