Paneth cell multi-potency induced by Notch activation following injury

Details

• Alternative Title:
  Cell Stem Cell
• Personal Author:
  Yu, Shiyan ; Tong, Kevin ; Zhao, Yanlin ; Balasubramanian, Iyshwarya ; Yap, George S. ; Ferraris, Ronaldo P. ; Bonder, Edward M. ; Verzi, Michael P. ; Gao, Nan
• Description:
  Paneth cells are post-mitotic intestinal epithelial cells supporting the stem cell niche and mucosal immunity. Paneth cell pathologies are observed in various gastrointestinal diseases, but their plasticity and response to genomic and environmental challenges remain unclear. Using a knockin allele engineered at the mouse Lyz1 locus, we performed detailed Paneth cell-lineage tracing. Irradiation induced a subset of Paneth cells to proliferate and differentiate into villus epithelial cells. RNA sequencing (RNA-seq) revealed that Paneth cells sorted from irradiated mice acquired a stem cell-like transcriptome; when cultured in vitro, these individual Paneth cells formed organoids. Irradiation activated Notch signaling, and forced expression of Notch intracellular domain (NICD) in Paneth cells, but not Wnt/β-catenin pathway activation, induced their dedifferentiation. This study documents Paneth cell plasticity, particularly their ability to participate in epithelial replenishment following stem cell loss, adding to a growing body of knowledge detailing the molecular pathways controlling injury-induced regeneration.
• Subjects:
  Article Intestinal Stem Cell Lysozyme Lyz1 Notch Paneth Cell Plasticity RNA-Seq Wnt
• Source:
  Cell Stem Cell. 23(1):46-59.e5
• Pubmed ID:
  29887318
• Pubmed Central ID:
  PMC6035085
• Document Type:
  Journal Article
• Funding:
  R21 CA178599/NCI NIH HHS/National Cancer Institute/United States ; R01 DK102934/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; R03 DK093809/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; S10 RR027022/NCRR NIH HHS/National Center for Research Resources/United States ; S10 OD018103/ODCDC CDC HHS/Office of the Director/United States ; R01 AI134040/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; R01 CA190558/NCI NIH HHS/National Cancer Institute/United States
• Volume:
  23
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:377090953da9f4f785b348953ebd25dd71f0bc4f8f7bd2145562b187497788be
• Download URL:
  https://stacks.cdc.gov/view/cdc/80574/cdc_80574_DS1.pdf
• File Type:
  [PDF - 1.72 MB ]