Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 1; pp. 179 - 184
• Main Authors: Montgomery, Robert K, Carlone, Diana L, Richmond, Camilla A, Farilla, Loredana, Kranendonk, Mariette E.G, Henderson, Daniel E, Baffour-Awuah, Nana Yaa, Ambruzs, Dana M, Fogli, Laura K, Algra, Selma, Breault, David T
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04-01-2011; National Acad Sciences
• Subjects: Animals; Biological Sciences; Cell Lineage - physiology; Cell lines; Cells; Crypts; Epithelial cells; Epithelium; Flow Cytometry; Gastroenterology; Gene expression; Genomes; Green Fluorescent Proteins - metabolism; HEK293 cells; Immunohistochemistry; Induced pluripotent stem cells; Injuries; Intestinal crypts; Intestinal Mucosa - cytology; Intestine; Intestines; Mice; Microscopy, Fluorescence; Multipotent Stem Cells - cytology; Multipotent Stem Cells - metabolism; Mutation; Receptors, G-Protein-Coupled - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Somatic cells; Stem cells; Telomerase; Telomerase - metabolism; telomerase reverse transcriptase
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1013004108

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.