Cell Stem Cell
Volume 23, Issue 1, 5 July 2018, Pages 46-59.e5
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Article
Paneth Cell Multipotency Induced by Notch Activation following Injury

https://doi.org/10.1016/j.stem.2018.05.002Get rights and content
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Highlights

  • Irradiation induced a subset of Paneth cells to acquire multipotency

  • Irradiated Paneth cells had a stem cell-like transcriptome and organoid-forming ability

  • Forced activation of the Notch pathway induced Paneth cell fate change

  • Constitutive activation of the Wnt/β-catenin pathway did not induce dedifferentiation

Summary

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.

Keywords

Paneth cell
intestinal stem cell
plasticity
Notch
lysozyme
Lyz1
Wnt
RNA-seq

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