Coinhibition of activated p38 MAPKα and mTORC1 potentiates stemness maintenance of HSCs from SR1-expanded human cord blood CD34⁺ cells via inhibition of senescence.

ABSTRACT: The stemness of ex vivo expanded hematopoietic stem cells (HSCs) is usually compromised by current methods. To explore the failure mechanism of stemness maintenance of human HSCs, which were expanded from human umbilical cord blood (hUCB) CD34⁺ cells, by differentiation inhibitor Stem Regenin 1 (SR1), an antagonist of aryl hydrocarbon receptor, we investigated the activity of p38 mitogen-activated protein kinase α (p38 MAPKα, p38α) and mammalian target of rapamycin complex 1 (mTORC1), and their effect on SR1-expanded hUCB CD34⁺ cells. Our results showed that cellular senescence occurred in the SR1-expanded hUCB CD34⁺ cells in which p38α and mTORC1 were successively activated. Furthermore, their coinhibition resulted in a further decrease in hUCB CD34^+<

SUBMITTER: Li X 

PROVIDER: S-EPMC7695631 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature