Literature DB >> 21297579

Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes.

Arnout G Schepers1, Robert Vries, Maaike van den Born, Marc van de Wetering, Hans Clevers.   

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.

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Year:  2011        PMID: 21297579      PMCID: PMC3061032          DOI: 10.1038/emboj.2011.26

Source DB:  PubMed          Journal:  EMBO J        ISSN: 0261-4189            Impact factor:   11.598


  33 in total

1.  The serial cultivation of human diploid cell strains.

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3.  Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation.

Authors:  R A Greenberg; R C Allsopp; L Chin; G B Morin; R A DePinho
Journal:  Oncogene       Date:  1998-04-02       Impact factor: 9.867

Review 4.  Stem cells in gastrointestinal epithelium: numbers, characteristics and death.

Authors:  C S Potten
Journal:  Philos Trans R Soc Lond B Biol Sci       Date:  1998-06-29       Impact factor: 6.237

5.  Telomerase activity concentrates in the mitotically active segments of human hair follicles.

Authors:  R D Ramirez; W E Wright; J W Shay; R S Taylor
Journal:  J Invest Dermatol       Date:  1997-01       Impact factor: 8.551

6.  Telomerase activity in human germline and embryonic tissues and cells.

Authors:  W E Wright; M A Piatyszek; W E Rainey; W Byrd; J W Shay
Journal:  Dev Genet       Date:  1996

7.  Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.

Authors:  G Cotsarelis; T T Sun; R M Lavker
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8.  Essential role of mouse telomerase in highly proliferative organs.

Authors:  H W Lee; M A Blasco; G J Gottlieb; J W Horner; C W Greider; R A DePinho
Journal:  Nature       Date:  1998-04-09       Impact factor: 49.962

9.  Specific association of human telomerase activity with immortal cells and cancer.

Authors:  N W Kim; M A Piatyszek; K R Prowse; C B Harley; M D West; P L Ho; G M Coviello; W E Wright; S L Weinrich; J W Shay
Journal:  Science       Date:  1994-12-23       Impact factor: 47.728

10.  Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts.

Authors:  G A Ulaner; J F Hu; T H Vu; L C Giudice; A R Hoffman
Journal:  Cancer Res       Date:  1998-09-15       Impact factor: 12.701

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  99 in total

1.  The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations.

Authors:  Kelley S Yan; Luis A Chia; Xingnan Li; Akifumi Ootani; James Su; Josephine Y Lee; Nan Su; Yuling Luo; Sarah C Heilshorn; Manuel R Amieva; Eugenio Sangiorgi; Mario R Capecchi; Calvin J Kuo
Journal:  Proc Natl Acad Sci U S A       Date:  2011-12-21       Impact factor: 11.205

2.  Organ aging and susceptibility to cancer may be related to the geometry of the stem cell niche.

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Journal:  Proc Natl Acad Sci U S A       Date:  2011-11-14       Impact factor: 11.205

3.  Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages.

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Journal:  J Anat       Date:  2011-12-05       Impact factor: 2.610

4.  Wnt signaling, stem cells, and cancer of the gastrointestinal tract.

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Journal:  Cold Spring Harb Perspect Biol       Date:  2012-04-01       Impact factor: 10.005

5.  The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers.

Authors:  Javier Muñoz; Daniel E Stange; Arnout G Schepers; Marc van de Wetering; Bon-Kyoung Koo; Shalev Itzkovitz; Richard Volckmann; Kevin S Kung; Jan Koster; Sorina Radulescu; Kevin Myant; Rogier Versteeg; Owen J Sansom; Johan H van Es; Nick Barker; Alexander van Oudenaarden; Shabaz Mohammed; Albert J R Heck; Hans Clevers
Journal:  EMBO J       Date:  2012-06-12       Impact factor: 11.598

6.  Optimality in the development of intestinal crypts.

Authors:  Shalev Itzkovitz; Irene C Blat; Tyler Jacks; Hans Clevers; Alexander van Oudenaarden
Journal:  Cell       Date:  2012-02-03       Impact factor: 41.582

Review 7.  When stem cells grow old: phenotypes and mechanisms of stem cell aging.

Authors:  Michael B Schultz; David A Sinclair
Journal:  Development       Date:  2016-01-01       Impact factor: 6.868

Review 8.  Understanding telomere diseases through analysis of patient-derived iPS cells.

Authors:  Luis F Z Batista; Steven E Artandi
Journal:  Curr Opin Genet Dev       Date:  2013-08-28       Impact factor: 5.578

Review 9.  Intestinal stem cells and the colorectal cancer microenvironment.

Authors:  Bryan A Ong; Kenneth J Vega; Courtney W Houchen
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Review 10.  A regulatory loop connecting WNT signaling and telomere capping: possible therapeutic implications for dyskeratosis congenita.

Authors:  Rafael Jesus Fernandez; F Brad Johnson
Journal:  Ann N Y Acad Sci       Date:  2018-04       Impact factor: 5.691

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