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Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal


When stem cells divide, they can generate progeny with the same developmental potential as the original cell, a process referred to as self-renewal. Self-renewal is driven intrinsically by gene expression in a cell-type-specific manner and is modulated through interactions with extrinsic cues from the environment, such as growth factors. However, despite the prevalence of the term self-renewal in the scientific literature, this process has not been defined at the molecular level. Haematopoietic stem cells are an excellent model for the study of self-renewal because they can be isolated prospectively, manipulated relatively easily and assessed by using well-defined assays. Establishing the principles of self-renewal in haematopoietic stem cells will lead to insights into the mechanisms of self-renewal in other tissues.

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Figure 1: Developmental signalling pathways involved in HSC self-renewal.
Figure 2: The Wnt-mediated signalling pathway modifies tissue regeneration.
Figure 3: Pathways that are involved in HSC homeostasis or in tissue regeneration can exhaust HSCs if activated frequently.
Figure 4: Hox genes can increase the self-renewal capacity of haematopoietic cells.


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I thank G. Sauvageau, S. Cellot and R. Bisaillon, R. Moon and C. Nerlov for providing figures. Work in my laboratory was supported by the Howard Hughes Medical Institute and grants from the National Institutes of Health.

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L.I.Z. is a founder of Fate Therapeutics.

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Zon, L. Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature 453, 306–313 (2008).

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