[PDF][PDF] Intestinal enteroendocrine lineage cells possess homeostatic and injury-inducible stem cell activity

KS Yan, O Gevaert, GXY Zheng, B Anchang… - Cell stem cell, 2017 - cell.com
KS Yan, O Gevaert, GXY Zheng, B Anchang, CS Probert, KA Larkin, PS Davies, Z Cheng
Cell stem cell, 2017cell.com
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 …
Summary
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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