Pluto Bioinformatics

GSE112358: The mediator subunit Med23 serves as a gatekeeper of the myeloid-primed state of hematopoietic stem cells (RNA-Seq)

Bulk RNA sequencing

To ensure the rapid response to stimuli, some HSCs are specifically prepared (primed) for tasks involving activation and reconstitution. However, the key factors that regulate the primed state of HSCs are largely unknown. Here we report that Med23 controls the formation of myeloid-primed HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Moreover, Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are in myeloid-primed state and are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is down-regulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identified Med23 as a gatekeeper of the myeloid-primed state of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid-primed state of HSCs and HSC activation upon stresses. SOURCE: Xufeng Chen (chenxufeng@sibcb.ac.cn) - Shanghai Institute of Biochemistry and Cell Biology, CAS