title: Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration.
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.
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xuxu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Chuang
authors.affiliation: Bioinformatics Core, Eugene McDermott Center for Human Growth & Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kanchwala
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Organ Transplant Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Cemre
authors.initials: C
authors.lastname: Celen
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Bioinformatics Core, Eugene McDermott Center for Human Growth & Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Hanquan
authors.initials: H
authors.lastname: Liang
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maples
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Liem H
authors.initials: LH
authors.lastname: Nguyen
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Sam C
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Robert A J
authors.initials: RA
authors.lastname: Signer
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Sorouri
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Nassour
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Mindich Child Health and Development Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: Mindich Child Health and Development Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Departments of Pharmacology and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Cardiac Surgery, Cardiovascular Research Center, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Bioinformatics Core, Eugene McDermott Center for Human Growth & Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Xing
authors.affiliation: Departments of Pediatrics and Internal Medicine, Children's Research Institute, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: hao.zhu@utsouthwestern.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008115:Liver Regeneration; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: C511511:Arid1a protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors