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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. and Krieger, K. and Klotz, C. and Krahn, I. and Kunz, S. and Kolesnichenko, M. and Mucka, P. and Heuberger, J. and 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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