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NF-κB determines Paneth versus goblet cell fate decision in the small intestine

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Item Type:Article
Title:NF-κB determines Paneth versus goblet cell fate decision in the small intestine
Creators Name:Brischetto, C., Krieger, K., Klotz, C., Krahn, I., Kunz, S., Kolesnichenko, M., Mucka, P., Heuberger, J., Scheidereit, C. and Schmidt-Ullrich, R.
Abstract:Although the role of the transcription factor NF-κB in intestinal inflammation and tumor formation has been investigated extensively, a physiological function of NF-κB in sustaining intestinal epithelial homeostasis beyond inflammation has not been demonstrated. Using NF-κB reporter mice, we detected strong NF-κB activity in Paneth cells, in '+4/+5' secretory progenitors and in scattered Lgr5+ crypt base columnar stem cells of small intestinal (SI) crypts. To examine NF-κB functions in SI epithelial self-renewal, mice or SI crypt organoids ('mini-guts') with ubiquitously suppressed NF-κB activity were used. We show that NF-κB activity is dispensable for maintaining SI epithelial proliferation, but is essential for ex vivo organoid growth. Furthermore, we demonstrate a dramatic reduction of Paneth cells in the absence of NF-κB activity, concomitant with a significant increase in goblet cells and immature intermediate cells. This indicates that NF-κB is required for proper Paneth versus goblet cell differentiation and for SI epithelial homeostasis, which occurs via regulation of Wnt signaling and Sox9 expression downstream of NF-κB. The current study thus presents evidence for an important role for NF-κB in intestinal epithelial self-renewal.
Keywords:NF-κB, Intestine, Paneth Cells, Goblet Cells, Stem Cells, Epithelial Self-Renewal, Animals, Mice
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists
Volume:148
Number:21
Page Range:dev199683
Date:November 2021
Official Publication:https://doi.org/10.1242/dev.199683
PubMed:View item in PubMed

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