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Publication : Paneth Cell Multipotency Induced by Notch Activation following Injury.

First Author  Yu S Year  2018
Journal  Cell Stem Cell Volume  23
Issue  1 Pages  46-59.e5
PubMed ID  29887318 Mgi Jnum  J:271577
Mgi Id  MGI:6278102 Doi  10.1016/j.stem.2018.05.002
Citation  Yu S, et al. (2018) Paneth Cell Multipotency Induced by Notch Activation following Injury. Cell Stem Cell 23(1):46-59.e5
abstractText  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/beta-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.
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