FANCD2 and HES1 suppress inflammation-induced PPARɣ to prevent haematopoietic stem cell exhaustion.

ABSTRACT: The Fanconi anaemia protein FANCD2 suppresses PPAR_Ɣ to maintain haematopoietic stem cell's (HSC) function; however, the underlying mechanism is not known. Here we show that FANCD2 acts in concert with the Notch target HES1 to suppress inflammation-induced PPAR_Ɣ in HSC maintenance. Loss of HES1 exacerbates FANCD2-KO HSC defects. However, deletion of HES1 does not cause more severe inflammation-mediated HSC defects in FANCD2-KO mice, indicating that both FANCD2 and HES1 are required for limiting detrimental effects of inflammation on HSCs. Further analysis shows that both FANCD2 and HES1 are required for transcriptional repression of inflammation-activated PPARg promoter. Inflammation orchestrates an overlapping transcriptional programme in HSPCs deficient for FANCD2 an

SUBMITTER: Wu L 

PROVIDER: S-EPMC7856217 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature