Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration

Xuxu Sun, Jen Chieh Chuang, Mohammed Kanchwala, Linwei Wu, Cemre Celen, Lin Li, Hanquan Liang, Shuyuan Zhang, Thomas Maples, Liem H. Nguyen, Sam C. Wang, Robert A J Signer, Mahsa Sorouri, Ibrahim Nassour, Xin Liu, Jian Xu, Meng Wu, Yong Zhao, Yi Chun Kuo, Zhong Wang & 2 others Chao Xing, Hao Zhu

Research output: Contribution to journalArticle

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Abstract

Mammals have partially lost the extensive regenerative capabilities of some vertebrates, possibly as a result of chromatin-remodeling mechanisms that enforce terminal differentiation. Here, we show that deleting the SWI/SNF component Arid1a substantially improves mammalian regeneration. Arid1a expression is suppressed in regenerating tissues, and genetic deletion of Arid1a increases tissue repair following an array of injuries. Arid1a deficiency in the liver increases proliferation, reduces tissue damage and fibrosis, and improves organ function following surgical resection and chemical injuries. Hepatocyte-specific deletion is also sufficient to increase proliferation and regeneration without excessive overgrowth, and global Arid1a disruption potentiates soft tissue healing in the ear. We show that Arid1a loss reprograms chromatin to restrict promoter access by transcription factors such as C/ebpα, which enforces differentiation, and E2F4, which suppresses cell-cycle re-entry. Thus, epigenetic reprogramming mediated by deletion of a single gene improves mammalian regeneration and suggests strategies to promote tissue repair after injury.

Original languageEnglish (US)
Pages (from-to)456-466
Number of pages11
JournalCell Stem Cell
Volume18
Issue number4
DOIs
StatePublished - Apr 7 2016

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Regeneration
Wounds and Injuries
Chromatin Assembly and Disassembly
Epigenomics
Chromatin
Ear
Vertebrates
Mammals
Hepatocytes
Cell Cycle
Fibrosis
Transcription Factors
Liver
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration. / Sun, Xuxu; Chuang, Jen Chieh; Kanchwala, Mohammed; Wu, Linwei; Celen, Cemre; Li, Lin; Liang, Hanquan; Zhang, Shuyuan; Maples, Thomas; Nguyen, Liem H.; Wang, Sam C.; Signer, Robert A J; Sorouri, Mahsa; Nassour, Ibrahim; Liu, Xin; Xu, Jian; Wu, Meng; Zhao, Yong; Kuo, Yi Chun; Wang, Zhong; Xing, Chao; Zhu, Hao.

In: Cell Stem Cell, Vol. 18, No. 4, 07.04.2016, p. 456-466.

Research output: Contribution to journalArticle

Sun, X, Chuang, JC, Kanchwala, M, Wu, L, Celen, C, Li, L, Liang, H, Zhang, S, Maples, T, Nguyen, LH, Wang, SC, Signer, RAJ, Sorouri, M, Nassour, I, Liu, X, Xu, J, Wu, M, Zhao, Y, Kuo, YC, Wang, Z, Xing, C & Zhu, H 2016, 'Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration', Cell Stem Cell, vol. 18, no. 4, pp. 456-466. https://doi.org/10.1016/j.stem.2016.03.001
Sun X, Chuang JC, Kanchwala M, Wu L, Celen C, Li L et al. Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration. Cell Stem Cell. 2016 Apr 7;18(4):456-466. https://doi.org/10.1016/j.stem.2016.03.001
Sun, Xuxu ; Chuang, Jen Chieh ; Kanchwala, Mohammed ; Wu, Linwei ; Celen, Cemre ; Li, Lin ; Liang, Hanquan ; Zhang, Shuyuan ; Maples, Thomas ; Nguyen, Liem H. ; Wang, Sam C. ; Signer, Robert A J ; Sorouri, Mahsa ; Nassour, Ibrahim ; Liu, Xin ; Xu, Jian ; Wu, Meng ; Zhao, Yong ; Kuo, Yi Chun ; Wang, Zhong ; Xing, Chao ; Zhu, Hao. / Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration. In: Cell Stem Cell. 2016 ; Vol. 18, No. 4. pp. 456-466.
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