Zeb1 sustains hematopoietic stem cell functions by suppressing mitofusin-2-mediated mitochondrial fusion.

ABSTRACT: Metabolic status is essential in maintaining normal functions of hematopoietic stem cells (HSCs). However, how the dynamic of the mitochondrion, as a central organelle in metabolism, is molecularly regulated to orchestrate metabolism and HSC stemness remains to be elucidated. Here, we focus on the role of Zeb1, a well-characterized epithelial-to-mesenchymal transition (EMT) inducer which has been demonstrated to confer stem-cell-like characteristics in multiple cancer types in stemness regulation of HSCs. Using a Zeb1-tdTomato reporter mouse model, we find that Zeb1⁺Lin^-Sca-1⁺c-Kit⁺ cells (Zeb1⁺-LSKs) represent a subset of functional long-term HSCs. Zeb1⁺LSKs exhibit a reduced reactive oxygen species (ROS) level, low mitocho

SUBMITTER: Zhang K 

PROVIDER: S-EPMC9411618 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature