1. Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity
- Author
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Yan, Kelley S, Gevaert, Olivier, Zheng, Grace XY, Anchang, Benedict, Probert, Christopher S, Larkin, Kathryn A, Davies, Paige S, Cheng, Zhuan-fen, Kaddis, John S, Han, Arnold, Roelf, Kelly, Calderon, Ruben I, Cynn, Esther, Hu, Xiaoyi, Mandleywala, Komal, Wilhelmy, Julie, Grimes, Sue M, Corney, David C, Boutet, Stéphane C, Terry, Jessica M, Belgrader, Phillip, Ziraldo, Solongo B, Mikkelsen, Tarjei S, Wang, Fengchao, von Furstenberg, Richard J, Smith, Nicholas R, Chandrakesan, Parthasarathy, May, Randal, Chrissy, Mary Ann S, Jain, Rajan, Cartwright, Christine A, Niland, Joyce C, Hong, Young-Kwon, Carrington, Jill, Breault, David T, Epstein, Jonathan, Houchen, Courtney W, Lynch, John P, Martin, Martin G, Plevritis, Sylvia K, Curtis, Christina, Ji, Hanlee P, Li, Linheng, Henning, Susan J, Wong, Melissa H, and Kuo, Calvin J
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Non-Human ,Regenerative Medicine ,Digestive Diseases ,1.1 Normal biological development and functioning ,Underpinning research ,Animals ,Antigens ,Differentiation ,Enteroendocrine Cells ,Gene Expression Regulation ,Intestinal Mucosa ,Jejunum ,Mice ,Mice ,Transgenic ,Stem Cells ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - 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.
- Published
- 2017