摘要：SummarySMCHD1 (structural maintenance of chromosomes hinge domain containing 1) is a noncanonical SMC protein that mediates long-range repressive chromatin structures. SMCHD1 is required for X chromosome inactivation in female cells and repression of imprinted and clustered autosomal genes, withSMCHD1mutations linked to human diseases facioscapulohumeral muscular dystrophy (FSHD) and bosma arhinia and micropthalmia syndrome (BAMS). We used a conditional mouse model to investigate SMCHD1 in hematopoiesis.Smchd1-deleted mice maintained steady-state hematopoiesis despite showing an impaired reconstitution capacity in competitive bone marrow transplantations and age-related hematopoietic stem cell (HSC) loss. This phenotype was more pronounced inSmchd1-deleted females, which showed a loss of quiescent HSCs and fewer B cells. Gene expression profiling ofSmchd1-deficient HSCs and B cells revealed known and cell-type-specific SMCHD1-sensitive genes and significant disruption to X-linked gene expression in female cells. These data show SMCHD1 is a regulator of HSCs whose effects are more profound in females.Graphical abstractDisplay OmittedHighlights•SMCHD1 is not required to maintain steady-state hematopoiesis•Smchd1-deletion leads to loss of adult hematopoietic stem cells•Smchd1-deleted female mice are more severely affected than males•SMCHD1 maintains cellular quiescence in female hematopoietic stem cellsMolecular biology; Cell biology; Stem cells research; Developmental biology.
