GSE112358
The mediator subunit Med23 serves as a gatekeeper of the myeloid-primed state of hematopoietic stem cells (RNA-Seq)
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. Overall design: Med23-deficient HSCs Vs WT HSCs. For RNAseq, We have 3 replicates for Med23-deficient cases, including KO1_RNA, KO2_RNA, KO3_RNA, as well as 3 replicates for wild type as controls, WT1_RNA, WT2_RNA, WT3_RNAseq. For ATAC, we have 2 replicates for med23 knockout cases, including KO1_ATAC, KO2_ATAC, as well as 2 replicates for wild type as controls, WT1_ATAC, WT2_ATAC.