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Notch2 governs the rate of generation of mouse long-and short-term repopulating stem cells
- Source :
- Journal of Clinical Investigation. March, 2011, Vol. 121 Issue 3, p1207, 10 p.
- Publication Year :
- 2011
-
Abstract
- HSCs either self-renew or differentiate to give rise to multipotent cells whose progeny provide blood cell precursors. However, surprisingly little is known about the factors that regulate this choice of self-renewal versus differentiation. One candidate is the Notch signaling pathway, with ex vivo studies suggesting that Notch regulates HSC differentiation, although a functional role for Notch in HSC self-renewal in vivo remains controversial. Here, we have shown that Notch2, and not Notch1, inhibits myeloid differentiation and enhances generation of primitive [Sca-1.sup.+]c-[kit.sup.+] progenitors following in vitro culture of enriched HSCs with purified Notch ligands. In mice, Notch2 enhanced the rate of formation of short-term repopulating multipotential progenitor cells (MPPs) as well as long-term repopulating HSCs, while delaying myeloid differentiation in BM following injury. However, consistent with previous reports, once homeostasis was achieved, neither Notch1 nor Notch2 affected repopulating cell self-renewal. These data indicate a Notch2-dependent role in assuring orderly repopulation by HSCs, MPPs, myeloid cells, and lymphoid cells during BM regeneration.<br />Introduction HSCs either self-renew or give rise to multipotent cells whose progeny provide precursors committed to the lymphoid and myeloid lineages. Recent studies have identified factors that maintain HSCs in [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 121
- Issue :
- 3
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.251194741
- Full Text :
- https://doi.org/10.1172/JCI43868