Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells.

ABSTRACT: Here, we show that the Wnt5a-haploinsufficient niche regenerates dysfunctional HSCs, which do not successfully engraft in secondary recipients. RNA sequencing of the regenerated donor Lin^- SCA-1⁺ KIT⁺ (LSK) cells shows dysregulated expression of ZEB1-associated genes involved in the small GTPase-dependent actin polymerization pathway. Misexpression of DOCK2, WAVE2, and activation of CDC42 results in apolar F-actin localization, leading to defects in adhesion, migration and homing of HSCs regenerated in a Wnt5a-haploinsufficient microenvironment. Moreover, these cells show increased differentiation in vitro, with rapid loss of HSC-enriched LSK cells. Our study further shows that the Wnt5a-haploinsufficient environment similarly affects BCR-ABL^p185

SUBMITTER: Schreck C 

PROVIDER: S-EPMC5206491 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature