Journal
CELL STEM CELL
Volume 25, Issue 1, Pages 54-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2019.06.008
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Funding
- Chinese Academy of Sciences [XDA16020201, XDA12050104]
- National Natural Science Foundation of China [31630044, 31601186, 81703093, 31801228]
- Science and Technology Commission of Shanghai Municipality [16JC1400202]
- National Major Science and Technology Projects of China [2018ZX09711002-009]
- National Special Support Plan for Top Talents
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Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. The intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed. Here we show that Arid1a, a key component of the SWI/SNF chromatin remodeling complex, controls liver regeneration and gene expression associated with emergence of injury-induced liver-progenitor-like cells (LPLCs). Hepatocyte-specific Arid1a ablation reduces LPLC gene expression in several models of periportal liver injury and impairs liver regeneration, leading to organ dysfunction. Arid1a establishes a permissive chromatin state at LPLC-enriched genes during homeostasis, suggesting it endows hepatocytes with competence to respond to injury-induced signals. Consistently, Arid1a facilitates binding of YAP, a critical regeneration signaling pathway, to LPLC-enriched genes, and Arid1a deletion prevents their YAP-associated induction following injury. Together, these findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration.
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