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Publication : Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.

First Author  Yan KS Year  2017
Journal  Cell Stem Cell Volume  21
Issue  1 Pages  78-90.e6
PubMed ID  28686870 Mgi Jnum  J:253992
Mgi Id  MGI:6101273 Doi  10.1016/j.stem.2017.06.014
Citation  Yan KS, et al. (2017) Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity. Cell Stem Cell 21(1):78-90.e6
abstractText  Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5(+) ISCs, the most well-defined ISC pool, but Bmi1-GFP(+) cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP(+) cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1(+) cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of Prox1-GFP(+) cells, one of which resembled mature EE cells while the other displayed low-level EE gene expression but co-expressed tuft cell markers, Lgr5 and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest that the EE lineage, including mature EE cells, comprises a reservoir of homeostatic and injury-inducible ISCs, extending our understanding of cellular plasticity and stemness.
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