| First Author | Varnum-Finney B | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 3 | Pages | 1207-16 |
| PubMed ID | 21285514 | Mgi Jnum | J:171820 |
| Mgi Id | MGI:5000159 | Doi | 10.1172/JCI43868 |
| Citation | Varnum-Finney B, et al. (2011) Notch2 governs the rate of generation of mouse long- and short-term repopulating stem cells. J Clin Invest 121(3):1207-16 |
| abstractText | 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(+)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. |
