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Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.
Yan, Kelley S; Gevaert, Olivier; Zheng, Grace X Y; 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; Kuo, Calvin J.
Afiliação
  • Yan KS; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Columbia Center for Human Development, Columbia Stem Cell Initiative, Department of Medicine, Division of Digestive and Liver Diseases, Department of Genetics and Development, Columbia University Medical Center,
  • Gevaert O; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Zheng GXY; 10x Genomics, Inc., Pleasanton, CA 94566, USA.
  • Anchang B; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Probert CS; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Larkin KA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Davies PS; Oregon Health & Science University, Department of Cell, Developmental and Cancer Biology, Portland, OR 97239, USA.
  • Cheng ZF; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Kaddis JS; Department of Diabetes and Cancer Discovery Science, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
  • Han A; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Columbia Center for Translational Immunology, Department of Medicine, Division of Digestive and Liver Diseases, Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032,
  • Roelf K; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Calderon RI; Columbia Center for Human Development, Columbia Stem Cell Initiative, Department of Medicine, Division of Digestive and Liver Diseases, Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Cynn E; Columbia Center for Human Development, Columbia Stem Cell Initiative, Department of Medicine, Division of Digestive and Liver Diseases, Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Hu X; Columbia Center for Human Development, Columbia Stem Cell Initiative, Department of Medicine, Division of Digestive and Liver Diseases, Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Mandleywala K; Columbia Center for Human Development, Columbia Stem Cell Initiative, Department of Medicine, Division of Digestive and Liver Diseases, Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Wilhelmy J; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Grimes SM; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Corney DC; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Boutet SC; 10x Genomics, Inc., Pleasanton, CA 94566, USA.
  • Terry JM; 10x Genomics, Inc., Pleasanton, CA 94566, USA.
  • Belgrader P; 10x Genomics, Inc., Pleasanton, CA 94566, USA.
  • Ziraldo SB; 10x Genomics, Inc., Pleasanton, CA 94566, USA.
  • Mikkelsen TS; 10x Genomics, Inc., Pleasanton, CA 94566, USA.
  • Wang F; Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
  • von Furstenberg RJ; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Smith NR; Oregon Health & Science University, Department of Cell, Developmental and Cancer Biology, Portland, OR 97239, USA.
  • Chandrakesan P; Department of Internal Medicine, Division of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • May R; Department of Internal Medicine, Division of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • Chrissy MAS; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Jain R; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Cartwright CA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Niland JC; Department of Diabetes and Cancer Discovery Science, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
  • Hong YK; Departments of Surgery and of Biochemistry & Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Carrington J; National Institutes of Health, Division of Digestive Diseases and Nutrition, NIDDK, Bethesda, MD 20892, USA.
  • Breault DT; Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Epstein J; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Houchen CW; Department of Internal Medicine, Division of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • Lynch JP; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Martin MG; Department of Pediatrics, Division of Gastroenterology and Nutrition, Mattel Children's Hospital and the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Plevritis SK; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Curtis C; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Ji HP; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Li L; Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
  • Henning SJ; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Wong MH; Oregon Health & Science University, Department of Cell, Developmental and Cancer Biology, Portland, OR 97239, USA.
  • Kuo CJ; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: cjkuo@stanford.edu.
Cell Stem Cell ; 21(1): 78-90.e6, 2017 07 06.
Article em En | MEDLINE | ID: mdl-28686870
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Antígenos de Diferenciação / Células Enteroendócrinas / Mucosa Intestinal / Jejuno Limite: Animals Idioma: En Revista: Cell Stem Cell Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Antígenos de Diferenciação / Células Enteroendócrinas / Mucosa Intestinal / Jejuno Limite: Animals Idioma: En Revista: Cell Stem Cell Ano de publicação: 2017 Tipo de documento: Article