PMID- 21173232 OWN - NLM STAT- MEDLINE DCOM- 20110210 LR - 20220318 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 108 IP - 1 DP - 2011 Jan 4 TI - Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. PG - 179-84 LID - 10.1073/pnas.1013004108 [doi] AB - The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5(+)) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+) cells. mTert-expressing cells distribute in a pattern along the crypt-villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that mTert(+) cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine. FAU - Montgomery, Robert K AU - Montgomery RK AD - Division of Gastroenterology, Children's Hospital Boston, Boston, MA 02115, USA. FAU - Carlone, Diana L AU - Carlone DL FAU - Richmond, Camilla A AU - Richmond CA FAU - Farilla, Loredana AU - Farilla L FAU - Kranendonk, Mariette E G AU - Kranendonk ME FAU - Henderson, Daniel E AU - Henderson DE FAU - Baffour-Awuah, Nana Yaa AU - Baffour-Awuah NY FAU - Ambruzs, Dana M AU - Ambruzs DM FAU - Fogli, Laura K AU - Fogli LK FAU - Algra, Selma AU - Algra S FAU - Breault, David T AU - Breault DT LA - eng GR - R01 DK 084056/DK/NIDDK NIH HHS/United States GR - R37 DK 32658/DK/NIDDK NIH HHS/United States GR - R01 DK084056/DK/NIDDK NIH HHS/United States GR - P30 HD 18655/HD/NICHD NIH HHS/United States GR - K08 DK066305/DK/NIDDK NIH HHS/United States GR - K08 DK 066305/DK/NIDDK NIH HHS/United States GR - R21 DK 078198/DK/NIDDK NIH HHS/United States GR - R37 DK032658/DK/NIDDK NIH HHS/United States GR - P30 HD018655/HD/NICHD NIH HHS/United States GR - P30 DK034854/DK/NIDDK NIH HHS/United States GR - P30 DK 34854/DK/NIDDK NIH HHS/United States GR - R21 DK078198/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20101220 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Lgr5 protein, mouse) RN - 0 (Receptors, G-Protein-Coupled) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.7.49 (Telomerase) RN - EC 2.7.7.49 (Tert protein, mouse) SB - IM MH - Animals MH - Cell Lineage/physiology MH - Flow Cytometry MH - Green Fluorescent Proteins/metabolism MH - Immunohistochemistry MH - Intestinal Mucosa/*cytology MH - Mice MH - Microscopy, Fluorescence MH - Multipotent Stem Cells/cytology/*metabolism MH - Receptors, G-Protein-Coupled/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Telomerase/*metabolism PMC - PMC3017192 COIS- The authors declare no conflict of interest. EDAT- 2010/12/22 06:00 MHDA- 2011/02/11 06:00 PMCR- 2011/07/04 CRDT- 2010/12/22 06:00 PHST- 2010/12/22 06:00 [entrez] PHST- 2010/12/22 06:00 [pubmed] PHST- 2011/02/11 06:00 [medline] PHST- 2011/07/04 00:00 [pmc-release] AID - 1013004108 [pii] AID - 201013004 [pii] AID - 10.1073/pnas.1013004108 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):179-84. doi: 10.1073/pnas.1013004108. Epub 2010 Dec 20.