TY - JOUR
T1 - Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity
AU - Yan, Kelley S.
AU - Gevaert, Olivier
AU - Zheng, Grace X.Y.
AU - Anchang, Benedict
AU - Probert, Christopher S.
AU - Larkin, Kathryn A.
AU - Davies, Paige S.
AU - Cheng, Zhuan fen
AU - Kaddis, John S.
AU - Han, Arnold
AU - Roelf, Kelly
AU - Calderon, Ruben I.
AU - Cynn, Esther
AU - Hu, Xiaoyi
AU - Mandleywala, Komal
AU - Wilhelmy, Julie
AU - Grimes, Sue M.
AU - Corney, David C.
AU - Boutet, Stéphane C.
AU - Terry, Jessica M.
AU - Belgrader, Phillip
AU - Ziraldo, Solongo B.
AU - Mikkelsen, Tarjei S.
AU - Wang, Fengchao
AU - von Furstenberg, Richard J.
AU - Smith, Nicholas R.
AU - Chandrakesan, Parthasarathy
AU - May, Randal
AU - Chrissy, Mary Ann S.
AU - Jain, Rajan
AU - Cartwright, Christine A.
AU - Niland, Joyce C.
AU - Hong, Young Kwon
AU - Carrington, Jill
AU - Breault, David T.
AU - Epstein, Jonathan
AU - Houchen, Courtney W.
AU - Lynch, John P.
AU - Martin, Martin G.
AU - Plevritis, Sylvia K.
AU - Curtis, Christina
AU - Ji, Hanlee P.
AU - Li, Linheng
AU - Henning, Susan J.
AU - Wong, Melissa H.
AU - Kuo, Calvin J.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/7/6
Y1 - 2017/7/6
N2 - 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. Multiple cell populations, represented by distinct markers including Lgr5 and Bmi1, are capable of reconstituting the intestinal epithelium. Using comparative RNA-sequencing and single-cell transcriptomics, Yan et al. define Bmi1-GFP+ and Prox1+ cells as enteroendocrine lineage cells that possess intestinal stem cell activity during homeostasis and injury-induced regeneration.
AB - 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. Multiple cell populations, represented by distinct markers including Lgr5 and Bmi1, are capable of reconstituting the intestinal epithelium. Using comparative RNA-sequencing and single-cell transcriptomics, Yan et al. define Bmi1-GFP+ and Prox1+ cells as enteroendocrine lineage cells that possess intestinal stem cell activity during homeostasis and injury-induced regeneration.
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U2 - 10.1016/j.stem.2017.06.014
DO - 10.1016/j.stem.2017.06.014
M3 - Article
C2 - 28686870
AN - SCOPUS:85029219708
SN - 1934-5909
VL - 21
SP - 78-90.e6
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -