Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity
Kelley S. Yan, Olivier Gevaert, Grace X.Y. Zheng, Benedict Anchang, Christopher S. Probert, Kathryn A. Larkin, Paige S. Davies, Zhuan-fen Cheng, John S. Kaddis, Arnold Han, Kelly Roelf, Ruben I. Calderon, Esther Cynn, Xiaoyi Hu, Komal Mandleywala, Julie Wilhelmy, Sue M. Grimes, David C. Corney, Stéphane C. Boutet, Jessica M. Terry, Phillip Belgrader, Solongo B. Ziraldo, Tarjei S. Mikkelsen, Fengchao Wang, Richard J. von Furstenberg, Nicholas R. Smith, Parthasarathy Chandrakesan, Randal May, Mary Ann S. Chrissy, Rajan Jain, Christine A. Cartwright, Joyce C. Niland, Young-Kwon Hong, Jill Carrington, David T. Breault, Jonathan Epstein, Courtney W. Houchen, John P. Lynch, Martin G. Martin, Sylvia K. Plevritis, Christina Curtis, Hanlee P. Ji, Linheng Li, Susan J. Henning, Melissa H. Wong, Calvin J. Kuo
文献索引：10.1016/j.stem.2017.06.014
全文：HTML全文
摘要
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, includingProx1. Prox1-GFP+cells exhibited sustained clonogenic growthin vitro, and lineage-tracing of Prox1+cells revealed long-lived clones during homeostasis and after radiation-induced injuryin 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,Lgr5andAscl2, 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.