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TGFB1 induces fetal reprogramming and enhances intestinal regeneration.
Chen, Lei; Qiu, Xia; Dupre, Abigail; Pellon-Cardenas, Oscar; Fan, Xiaojiao; Xu, Xiaoting; Rout, Prateeksha; Walton, Katherine D; Burclaff, Joseph; Zhang, Ruolan; Fang, Wenxin; Ofer, Rachel; Logerfo, Alexandra; Vemuri, Kiranmayi; Bandyopadhyay, Sheila; Wang, Jianming; Barbet, Gaetan; Wang, Yan; Gao, Nan; Perekatt, Ansu O; Hu, Wenwei; Magness, Scott T; Spence, Jason R; Verzi, Michael P.
Afiliação
  • Chen L; School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China. Electronic address: leichen@seu.edu.cn.
  • Qiu X; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Dupre A; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Pellon-Cardenas O; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Fan X; School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
  • Xu X; School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
  • Rout P; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Walton KD; Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Burclaff J; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, and North Carolina State University, Chapel Hill, NC 27695, USA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
  • Zhang R; School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
  • Fang W; School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
  • Ofer R; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Logerfo A; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Vemuri K; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA.
  • Bandyopadhyay S; Department of Biological Sciences, Rutgers University-Newark, Newark, NJ 07102, USA.
  • Wang J; Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University-New Brunswick, New Brunswick, NJ 08903, USA.
  • Barbet G; Child Health Institute of New Jersey, Rutgers University-New Brunswick, New Brunswick, NJ 08901, USA.
  • Wang Y; Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
  • Gao N; Department of Biological Sciences, Rutgers University-Newark, Newark, NJ 07102, USA.
  • Perekatt AO; Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
  • Hu W; Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University-New Brunswick, New Brunswick, NJ 08903, USA.
  • Magness ST; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, and North Carolina State University, Chapel Hill, NC 27695, USA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
  • Spence JR; Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan
  • Verzi MP; Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 00854, USA; Rutgers Cancer Institute of New Jersey, Rutgers University-New Brunswick, New Brunswick, NJ 08903, USA; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Heal
Cell Stem Cell ; 30(11): 1520-1537.e8, 2023 11 02.
Article em En | MEDLINE | ID: mdl-37865088
ABSTRACT
The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mucosa Intestinal / Intestinos Limite: Animals / Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mucosa Intestinal / Intestinos Limite: Animals / Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2023 Tipo de documento: Article