Journal
CELL STEM CELL
Volume 21, Issue 1, Pages 78-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2017.06.014
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Categories
Funding
- CIRM MD Scholars Fellowship
- NIH [K08DK096048, K08DK100739]
- Burroughs Wellcome Fund Career Award for Medical Scientists
- NSF [DGE-114747]
- BWF CAMS
- WW Smith Foundation
- Timothy Murphy Fund
- IDDRC [P30HD18655]
- HDDC [P30DK034854]
- NIH Intestinal Stem Cell Consortium - NIDDK
- NIAID [UO1DK085547, U01DK085525, U01DK085532, U01DK085508, U01DK085535, U01DK085551, U01DK085507, U01DK085527]
- [U54CA209971]
- [R01DK084056]
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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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