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

Abstract:

: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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Yan KS,Gevaert O,Zheng GXY,Anchang B,Probert CS,Larkin KA,Davies PS,Cheng ZF,Kaddis JS,Han A,Roelf K,Calderon RI,Cynn E,Hu X,Mandleywala K,Wilhelmy J,Grimes SM,Corney DC,Boutet SC,Terry JM,Belgrader P,Ziraldo SB

doi

10.1016/j.stem.2017.06.014

subject

Has Abstract

pub_date

2017-07-06 00:00:00

pages

78-90.e6

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(17)30240-0

journal_volume

21

pub_type

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