TY - JOUR
T1 - The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow
AU - Shao, Lijian
AU - Chang, Jianhui
AU - Feng, Wei
AU - Wang, Xiaoyan
AU - Williamson, Elizabeth A.
AU - Li, Ying
AU - Schajnovitz, Amir
AU - Scadden, David
AU - Mortensen, Luke J.
AU - Lin, Charles P.
AU - Li, Linheng
AU - Paulson, Ariel
AU - Downing, James
AU - Zhou, Daohong
AU - Hromas, Robert A.
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-018-04716-5
DO - 10.1038/s41467-018-04716-5
M3 - Article
C2 - 29915352
AN - SCOPUS:85048811758
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2377
ER -