| Autor: |
Celen, Cemre, Chuang, Jen-Chieh, Shen, Shunli, Li, Lin, Maggiore, Gianna, Jia, Yuemeng, Luo, Xin, Moore, Austin, Wang, Yunguan, Otto, Jordan E., Collings, Clayton K., Wang, Zixi, Sun, Xuxu, Nassour, Ibrahim, Park, Jiyoung, Ghaben, Alexandra, Wang, Tao, Wang, Sam C., Scherer, Philipp E., Kadoch, Cigall, Zhu, Hao |
| Zdroj: |
Cell Reports; November 2022, Vol. 41 Issue: 5 |
| Abstrakt: |
The dynamic regulation of β-cell abundance is poorly understood. Since chromatin remodeling plays critical roles in liver regeneration, these mechanisms could be generally important for regeneration in other tissues. Here, we show that the ARID1A mammalian SWI/SNF complex subunit is a critical regulator of β-cell regeneration. Arid1ais highly expressed in quiescent β-cells but is physiologically suppressed when β-cells proliferate during pregnancy or after pancreas resection. Whole-body Arid1aknockout mice are protected against streptozotocin-induced diabetes. Cell-type and temporally specific genetic dissection show that β-cell-specific Arid1adeletion can potentiate β-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets reveal increased neuregulin-ERBB-NR4A signaling. Chemical inhibition of ERBB or NR4A1 blocks increased regeneration associated with Arid1aloss. Mammalian SWI/SNF (mSWI/SNF) complex activity is a barrier to β-cell regeneration in physiologic and disease states. |
| Databáze: |
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