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PLoS Genet. 2017 Jun 29;13(6):e1006854. doi: 10.1371/journal.pgen.1006854. eCollection 2017 Jun.

A genetic framework controlling the differentiation of intestinal stem cells during regeneration in Drosophila.

Author information

1
Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, Lausanne, Switzerland.

Abstract

The speed of stem cell differentiation has to be properly coupled with self-renewal, both under basal conditions for tissue maintenance and during regeneration for tissue repair. Using the Drosophila midgut model, we analyze at the cellular and molecular levels the differentiation program required for robust regeneration. We observe that the intestinal stem cell (ISC) and its differentiating daughter, the enteroblast (EB), form extended cell-cell contacts in regenerating intestines. The contact between progenitors is stabilized by cell adhesion molecules, and can be dynamically remodeled to elicit optimal juxtacrine Notch signaling to determine the speed of progenitor differentiation. Notably, increasing the adhesion property of progenitors by expressing Connectin is sufficient to induce rapid progenitor differentiation. We further demonstrate that JAK/STAT signaling, Sox21a and GATAe form a functional relay to orchestrate EB differentiation. Thus, our study provides new insights into the complex and sequential events that are required for rapid differentiation following stem cell division during tissue replenishment.

PMID:
28662029
PMCID:
PMC5510897
DOI:
10.1371/journal.pgen.1006854
[Indexed for MEDLINE]
Free PMC Article

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