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- Title
The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.
- Authors
Lijian Shao; Jianhui Chang; Wei Feng; Xiaoyan Wang; Williamson, Elizabeth A.; Ying Li; Schajnovitz, Amir; Scadden, David; Mortensen, Luke J.; Lin, Charles P.; Linheng Li; Paulson, Ariel; Downing, James; Daohong Zhou; Hromas, Robert A.
- 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 verprolinhomologous 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.
- Subjects
HEMATOPOIESIS; BONE marrow; HEMATOPOIETIC stem cells; LIVER; WISKOTT-Aldrich syndrome; EARLY death
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04716-5