Comprehensive Analysis of Epigenetic Regulatory Network in the Mouse Incisor

Epigenetic regulation plays a crucial role in controlling the expression of stage- and tissue-specific genes during development and tissue homeostasis. As a core subunit of the BAF complex, ARID1B acts as a DNA-binding protein that regulates chromatin accessibility. However, the role of ARID1B as an epigenetic regulator in maintaining adult stem cell homeostasis remains largely unexplored. In this study, we used the continuously growing mouse incisor as a model to investigate the role of ARID1B in regulating mesenchymal stem cell (MSC) homeostasis and cell fate commitment. Our findings demonstrate that loss of ARID1B within the Gli1+ MSC lineage impairs mouse incisor growth and tissue homeostasis. Through comprehensive analysis of single-cell (sc)RNA-seq, scATAC-seq, and bulk RNA-seq data, we identified BCL11B as a direct downstream gene of ARID1B. Our study highlights the critical roles of ARID1B in maintaining MSC homeostasis and its intricate interaction with non-Smad TGF-β signaling, providing valuable insights into the epigenetic regulatory network and its potential implications for stem cell regulation in the future.