Shao, LijianChang, JianhuiFeng, WeiWang, XiaoyanWilliamson, Elizabeth A.Li, YingSchajnovitz, AmirScadden, DavidMortensen, Luke J.Lin, CharlesLi, LinhengPaulson, ArielDowning, JamesZhou, DaohongHromas, Robert A.2018-07-252018Shao, L., J. Chang, W. Feng, X. Wang, E. A. Williamson, Y. Li, A. Schajnovitz, et al. 2018. “The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.” Nature Communications 9 (1): 2377. doi:10.1038/s41467-018-04716-5. http://dx.doi.org/10.1038/s41467-018-04716-5.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37298484The transition of hematopoiesis from the fetal liver (FL) to the bone marrow (BM) is incompletely characterized. We demonstrate that the Wiskott–Aldrich syndrome verprolin-homologous protein (WAVE) complex 2 is required for this transition, as complex degradation via deletion of its scaffold Hem-1 causes the premature exhaustion of neonatal BM hematopoietic stem cells (HSCs). This exhaustion of BM HSC is due to the failure of BM engraftment of Hem-1−/− FL HSCs, causing early death. The Hem-1−/− FL HSC engraftment defect is not due to the lack of the canonical function of the WAVE2 complex, the regulation of actin polymerization, because FL HSCs from Hem-1−/− mice exhibit no defects in chemotaxis, BM homing, or adhesion. Rather, the failure of Hem-1−/− FL HSC engraftment in the marrow is due to the loss of c-Abl survival signaling from degradation of the WAVE2 complex. However, c-Abl activity is dispensable for the engraftment of adult BM HSCs into the BM. These findings reveal a novel function of the WAVE2 complex and define a mechanism for FL HSC fitness in the embryonic BM niche.en-USJournal Article2018-07-2510.1038/s41467-018-04716-5