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Nat Commun. 2018 Jun 18;9(1):2377. doi: 10.1038/s41467-018-04716-5.

The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.

Author information

1
Department of Pharmacology, University of Illinois Chicago, Chicago, IL, 60612, USA.
2
Department of Pharmaceutical Sciences and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
3
Department of Medicine and Pathology, University of Florida, Gainesville, FL, 32610, USA.
4
Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, 02138, MA, USA.
5
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, 02114, MA, USA.
6
Harvard Stem Cell Institute, Cambridge, MA, 02138, USA.
7
Regenerative Medicine Center, University of Georgia, Athens, GA, 30602, USA.
8
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
9
Department of Pathology and Laboratory, Medicine University of Kansas, Kansas City, 66160, KA, USA.
10
Stowers Institute for Medical Research, Kansas City, MO, 66160, USA.
11
Department of Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
12
Department of Pharmaceutical Sciences and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. zhoudaohong@cop.ufl.edu.
13
Department of Pharmacodynamics, University of Florida, Gainesville, FL, 32610, USA. zhoudaohong@cop.ufl.edu.
14
Office of the Dean and the Cancer Center, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX, 78229, USA. hromas@uthscsa.edu.

Abstract

The 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.

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