期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 3, 页码 1207-1216出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI43868
关键词
-
资金
- NIH [PO1 HL084205]
- F.M. Kirby Foundation
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 Notch 1, inhibits myeloid differentiation and enhances generation of primitive Sca-1(+)c-kit(+) 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.
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