PMID- 27799368 OWN - NLM STAT- MEDLINE DCOM- 20170531 LR - 20240922 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 215 IP - 3 DP - 2016 Nov 7 TI - Msi RNA-binding proteins control reserve intestinal stem cell quiescence. PG - 401-413 AB - Regeneration of the intestinal epithelium is driven by multiple intestinal stem cell (ISC) types, including an active, radiosensitive Wnt(high) ISC that fuels turnover during homeostasis and a reserve, radioresistant Wnt(low/off) ISC capable of generating active Wnt(high) ISCs. We examined the role of the Msi family of oncoproteins in the ISC compartment. We demonstrated that Msi proteins are dispensable for normal homeostasis and self-renewal of the active ISC, despite their being highly expressed in these cells. In contrast, Msi proteins are required specifically for activation of reserve ISCs, where Msi activity is both necessary and sufficient to drive exit from quiescence and entry into the cell cycle. Ablation of Msi activity in reserve ISCs rendered the epithelium unable to regenerate in response to injury that ablates the active stem cell compartment. These findings delineate a molecular mechanism governing reserve ISC quiescence and demonstrate a necessity for the activity of this rare stem cell population in intestinal regeneration. CI - (c) 2016 Yousefi et al. FAU - Yousefi, Maryam AU - Yousefi M AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. AD - Cell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104. FAU - Li, Ning AU - Li N AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. FAU - Nakauka-Ddamba, Angela AU - Nakauka-Ddamba A AUID- ORCID: 0000-0002-4631-7105 AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. FAU - Wang, Shan AU - Wang S AUID- ORCID: 0000-0002-0429-8890 AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. AD - State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100083, China. FAU - Davidow, Kimberly AU - Davidow K AUID- ORCID: 0000-0003-0597-5475 AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. FAU - Schoenberger, Jenna AU - Schoenberger J AUID- ORCID: 0000-0003-4278-669X AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. FAU - Yu, Zhengquan AU - Yu Z AUID- ORCID: 0000-0001-8696-2013 AD - State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100083, China. FAU - Jensen, Shane T AU - Jensen ST AD - Department of Biostatistics, the Wharton School, University of Pennsylvania, Philadelphia, PA 19104. FAU - Kharas, Michael G AU - Kharas MG AUID- ORCID: 0000-0002-1165-6991 AD - Molecular Pharmacology and Chemistry Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. FAU - Lengner, Christopher J AU - Lengner CJ AUID- ORCID: 0000-0002-0574-5189 AD - Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 lengner@vet.upenn.edu. AD - Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. AD - Cell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104. AD - Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104. LA - eng GR - P30 CA015704/CA/NCI NIH HHS/United States GR - P30 DK050306/DK/NIDDK NIH HHS/United States GR - R01 DK101989/DK/NIDDK NIH HHS/United States GR - R01 CA168654/CA/NCI NIH HHS/United States GR - R01 CA193842/CA/NCI NIH HHS/United States GR - R01 DK106309/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20161031 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Msi1h protein, mouse) RN - 0 (Msi2h protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA-Binding Proteins) SB - IM MH - Animals MH - Cell Lineage/radiation effects MH - Cell Proliferation/radiation effects MH - Epithelium/pathology/radiation effects MH - Gamma Rays MH - Homeostasis/radiation effects MH - Intestines/*cytology MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/*metabolism MH - RNA-Binding Proteins/*metabolism MH - Radiation Injuries/pathology MH - Resting Phase, Cell Cycle/radiation effects MH - S Phase/radiation effects MH - Stem Cells/*cytology/*metabolism/radiation effects MH - Up-Regulation/radiation effects MH - Wnt Signaling Pathway/radiation effects PMC - PMC5100293 EDAT- 2016/11/02 06:00 MHDA- 2017/06/01 06:00 PMCR- 2017/05/07 CRDT- 2016/11/02 06:00 PHST- 2016/04/27 00:00 [received] PHST- 2016/08/12 00:00 [revised] PHST- 2016/09/29 00:00 [accepted] PHST- 2016/11/02 06:00 [pubmed] PHST- 2017/06/01 06:00 [medline] PHST- 2016/11/02 06:00 [entrez] PHST- 2017/05/07 00:00 [pmc-release] AID - jcb.201604119 [pii] AID - 201604119 [pii] AID - 10.1083/jcb.201604119 [doi] PST - ppublish SO - J Cell Biol. 2016 Nov 7;215(3):401-413. doi: 10.1083/jcb.201604119. Epub 2016 Oct 31.