» Articles » PMID: 21297579

Lgr5 Intestinal Stem Cells Have High Telomerase Activity and Randomly Segregate Their Chromosomes

Overview
Journal EMBO J
Date 2011 Feb 8
PMID 21297579
Citations 117
Authors
Affiliations
Soon will be listed here.
Abstract

Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse, yet divide every day. We now demonstrate biochemically that primary isolated Lgr5+ve stem cells contain significant telomerase activity. Telomerase activity rapidly decreases in the undifferentiated progeny of these stem cells and is entirely lost in differentiated villus cells. Conversely, asymmetric segregation of chromosomes has been proposed as a mechanism for stem cells to protect their genomes against damage. We determined the average cell cycle length of Lgr5+ve stem cells at 21.5 h and find that Lgr5+ve intestinal stem cells randomly segregate newly synthesized DNA strands, opposing the 'immortal strand' hypothesis.

Citing Articles

Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.

Kappler M, Thielemann L, Glass M, Caggegi L, Guttler A, Pyko J Int J Mol Sci. 2025; 25(24.

PMID: 39769183 PMC: 11678308. DOI: 10.3390/ijms252413417.


Preparing Chamber Slides With Pressed Collagen for Live Imaging Monolayers of Primary Human Intestinal Stem Cells.

Burclaff J, Magness S Bio Protoc. 2024; 14(22):e5116.

PMID: 39600970 PMC: 11588582. DOI: 10.21769/BioProtoc.5116.


Cellular and molecular mechanisms of asymmetric stem cell division in tissue homeostasis.

Bolkent S Genes Cells. 2024; 29(12):1099-1110.

PMID: 39379096 PMC: 11609605. DOI: 10.1111/gtc.13172.


An in vitro platform for quantifying cell cycle phase lengths in primary human intestinal epithelial cells.

Cotton M, Ariel P, Chen K, Walcott V, Dixit M, Breau K Sci Rep. 2024; 14(1):15195.

PMID: 38956443 PMC: 11219882. DOI: 10.1038/s41598-024-66042-9.


Molecular mechanisms of aging and anti-aging strategies.

Li Y, Tian X, Luo J, Bao T, Wang S, Wu X Cell Commun Signal. 2024; 22(1):285.

PMID: 38790068 PMC: 11118732. DOI: 10.1186/s12964-024-01663-1.


References
1.
Montgomery R, Carlone D, Richmond C, Farilla L, Kranendonk M, Henderson D . Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci U S A. 2010; 108(1):179-84. PMC: 3017192. DOI: 10.1073/pnas.1013004108. View

2.
Flores I, Canela A, Vera E, Tejera A, Cotsarelis G, Blasco M . The longest telomeres: a general signature of adult stem cell compartments. Genes Dev. 2008; 22(5):654-67. PMC: 2259034. DOI: 10.1101/gad.451008. View

3.
Wright W, Piatyszek M, Rainey W, Byrd W, Shay J . Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996; 18(2):173-9. DOI: 10.1002/(SICI)1520-6408(1996)18:2<173::AID-DVG10>3.0.CO;2-3. View

4.
Ireland H, Houghton C, Howard L, Winton D . Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine. Dev Dyn. 2005; 233(4):1332-6. DOI: 10.1002/dvdy.20446. View

5.
Kiel M, He S, Ashkenazi R, Gentry S, Teta M, Kushner J . Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature. 2007; 449(7159):238-42. PMC: 2633872. DOI: 10.1038/nature06115. View