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Publication

Paneth Cell Multipotency Induced by Notch Activation following Injury.

Cell stem cell | 2018

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.

Pubmed ID: 29887318 RIS Download

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Associated grants

Agency: NCI NIH HHS, United States
Id: F32 CA235829
Agency: NCI NIH HHS, United States
Id: R21 CA178599
Agency: NIDDK NIH HHS, United States
Id: R01 DK102934
Agency: NIDDK NIH HHS, United States
Id: R03 DK093809
Agency: NIH HHS, United States
Id: S10 OD018103
Agency: NCI NIH HHS, United States
Id: R01 CA190558
Agency: NCRR NIH HHS, United States
Id: S10 RR027022
Agency: National Institute of Allergy and Infectious Diseases Extramural Activities, United States
Id: R01 AI134040

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RRID:SCR_000306

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