Abstract
Individual subunits within the canonical BAF (cBAF) chromatin remodeling complex are known to regulate stem cell behavior, with some functional redundancy across subunits. Yet, how the cBAF complex directs adult stem cell fate specification and maintains stem cell niches remains unclear. Using the adult mouse incisor, we show that cBAF specifies mesenchymal stem cell (MSC) fate by recruiting distinct transcriptional co-factors to shape cell-type-specific chromatin regulation. Through single-cell multi-omics and in vivo functional analyses, we identify ARID1-containing cBAF as an essential gatekeeper that maintains the dynamic balance between MSC self-renewal and differentiation. Specifically, cBAF–DLX2 interactions preserve niche identity by remodeling intronic chromatin accessibility of niche-defining marker Runx2, while cBAF–FOXO1 directly modulates promoter accessibility of lineage-regulating transcription factors, including STAT3 and TRP53, among others, to balance progenitor proliferation and differentiation. Functional perturbation of RUNX2 and TRP53 confirms their roles downstream of cBAF in niche maintenance and fate specification. Our findings establish cBAF as a central regulator of adult stem cell niches and lineage commitment, and highlight cofactor-dependent mechanisms that may have broader implications for tissue regeneration and BAF-associated disorders.
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Data availability
The raw and processed single-cell RNA sequencing (scRNA-seq), scATAC-seq, CUT&RUN-seq, and RNA-seq data generated in this study have been deposited in the Gene Expression Omnibus (GEO) under accession GSE314753. The control scRNA-seq, scATAC-seq, and RNA-seq data used in this study are available in the GEO database under accession code GSE237305. Data analyses were performed using Seurat v5 (https://satijalab.org/seurat/, https://doi.org/10.1038/s41587-023-01767-y) for scRNA-seq data and Signac (https://stuartlab.org/signac/, https://doi.org/10.1038/s41592-021-01282-5) for scATAC-seq data. Source data are provided with this paper.
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Acknowledgements
We are grateful to Dr. Bridget Samuels for critical reading and editing of the manuscript and to Ashley "Kimi" Nakaki for the schematic drawing of the mouse incisor. We acknowledge the USC Office of Research and the Norris Medical Library for providing bioinformatics software and computing resources, and the Technology Center for Genomics & Bioinformatics (TCGB) at the University of California, Los Angeles, for their sequencing-related service and support. This study was supported by grant funding from the National Institute of Dental and Craniofacial Research, National Institutes of Health (R01 DE025221 to YC).
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M.Z. and Y.C. designed the study; M.Z. carried out most of the experiments and data analysis; J.F. and T.G. provided critical suggestions and comments; L.M., F.P., L.G., Y.Y., and T.-V.H. participated in experiment preparation. M.Z. and Y.C. co-wrote the paper. Y.C. supervised the research.
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Zhang, M., Feng, J., Guo, T. et al. Canonical BAF chromatin remodeling complex specifies stem cell fate via cell-type-specific co-factor recruitment. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70038-6
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DOI: https://doi.org/10.1038/s41467-026-70038-6
