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Cell Stem Cell. 2018 Jul 5;23(1):46-59.e5. doi: 10.1016/j.stem.2018.05.002. Epub 2018 Jun 7.

Paneth Cell Multipotency Induced by Notch Activation following Injury.

Author information

1
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
2
Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.
3
Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101, USA.
4
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ 07101, USA.
5
Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
6
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. Electronic address: ngao@rutgers.edu.

Abstract

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:

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

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