摘要：SummaryZinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found thatZfp521deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast,Zfp521-null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed thatZfp521regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically,Zfp521transcriptionally repressedRelaexpression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown ofRelainhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence inZfp521-null HSC under stress. Thus, our results reveal a previously unrecognized role forZfp521as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controllingRelaexpression.Graphical abstractDisplay OmittedHighlights•Zfp521deletion does not inhibit adult hematopoiesis under homeostatic conditions•Zfp521regulates the quiescence and maintenance of HSC under stress•Zfp521deficiency affects the NF-κB pathway in HSC•Knockdown ofRelareverses the loss of quiescence in Zfp521-null HSC under stressMolecular Biology; Cell Biology; Stem Cell Research; Transcriptomics
