Canonical BAF complex orchestrates mesenchymal stem cell niche composition and fate via cofactor-guided chromatin remodeling [CUT&Run]
The canonical BAF (BRG1/BRM-associated factor) chromatin remodeling complex plays a pivotal role in governing stem cell behavior, yet how it regulates adult stem cell niche remains unclear. Here, we show that ARID1-containing cBAF complex orchestrates the spatial organization of the mesenchymal stem cell niche and fate in the adult mouse incisor. Dual loss of ARID1A and ARID1B in Gli1+ mesenchymal stem cells using conditional knockout mouse models disturbs chromatin accessibility in a cell-type-specific manner and alters cofactor recruitment, leading to niche cell disorganization, disrupting progenitor cells (transit-amplifying cells, TACs) fate commitment during tissue homeostasis. Single-cell multi-omics profiling and in vivo functional validations reveal that the cBAF complex partners with DLX2 to coordinate niche cell composition and recruits FOXO1 and DLX2 to balance TAC proliferation and differentiation. Our findings establish cBAF as a master regulator of chromatin state and microenvironment architecture, essential for maintaining adult mesenchymal stem cell function and tissue homeostasis. Overall design: Control mouse incisor proximal end tissue were collected and digested into cells, then underwent the process following the CUT&RUN protocol.