Evidence map›Paper›PMID 26584619›Full record

ArticleGenes & development2015

High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells.

Matthew F Pech, Alina Garbuzov, Kazuteru Hasegawa, Meena Sukhwani, Ruixuan J Zhang, Bérénice A Benayoun, Stephanie A Brockman, Shengda Lin, Anne Brunet, Kyle E Orwig and 1 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Review
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  12. Article
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  14. Article
  15. Telomere Length Regulation.Frontiers in oncology · 2022
    Review
  16. Article
  17. Molding immortality from a plastic germline.Current opinion in cell biology · 2021
    Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Matthew F PechDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA; Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA;
Alina GarbuzovDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA; Department of Genetics, Stanford University, California 94305, USA;
Kazuteru HasegawaDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
Meena SukhwaniDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh Pennsylvania 15213, USA; Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA;
Ruixuan J ZhangDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
Bérénice A BenayounDepartment of Genetics, Stanford University, California 94305, USA;
Stephanie A BrockmanDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
Shengda LinDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
Anne BrunetDepartment of Genetics, Stanford University, California 94305, USA;
Kyle E OrwigDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh Pennsylvania 15213, USA; Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA;
Steven E ArtandiDepartment of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA; Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA.
Stanford University · USMagee-Womens Research Institute · USUniversity of Pittsburgh · US

Funding

Wnt signaling in muscle stem cell agingP01AG036695 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARGARET A. GOODELL · 2011 to 2026
$29.3M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
GENETICS TRAINING PROGRAM FOR PHD CANDIDATEST32GM007790 · NIGMS · STANFORD UNIVERSITY · PI BRUNET, ANNE, KINGSLEY, DAVID M · 1985 to 2020
$12.8M
REVERSING CELLULAR IMMORTALITY IN CANCERR35CA197563 · NCI · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2015 to 2021
$6.4M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2011 to 2019
$6.3M
Telomeres, Telomerase and Tumor ProgressionR01CA111691 · NCI · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2005 to 2015
$2.8M
Regulation of the Telomerase Protein Component In CancerR01CA125453 · NCI · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2006 to 2015
$2.2M
Defining the telomerase holoenzyme in progenitor cells with agingR01AG033747 · NIA · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2010 to 2014
$1.6M
Defining the telomerase holoenzyme in progenitor cells with agingR56AG033747 · NIA · STANFORD UNIVERSITY · PI ARTANDI, STEVEN E · 2016 to 2016
$597k
NCI NIH HHS CA09302NCI NIH HHS CA111691NCI NIH HHS CA125453NCI NIH HHS R01 CA111691NCI NIH HHS R01 CA125453NCI NIH HHS R35 CA197563NCI NIH HHS T32 CA009302NIA NIH HHS AG033747NIA NIH HHS AG036695NIA NIH HHS P01 AG036695NIA NIH HHS R01 AG033747NIA NIH HHS R56 AG033747NINDS NIH HHS NS069375NINDS NIH HHS P30 NS069375
6 · The paper itself

Abstract

Telomerase inactivation causes loss of the male germline in worms, fish, and mice, indicating a conserved dependence on telomere maintenance in this cell lineage. Here, using telomerase reverse transcriptase (Tert) reporter mice, we found that very high telomerase expression is a hallmark of undifferentiated spermatogonia, the mitotic population where germline stem cells reside. We exploited these high telomerase levels as a basis for purifying undifferentiated spermatogonia using fluorescence-activated cell sorting. Telomerase levels in undifferentiated spermatogonia and embryonic stem cells are comparable and much greater than in somatic progenitor compartments. Within the germline, we uncovered an unanticipated gradient of telomerase activity that also enables isolation of more mature populations. Transcriptomic comparisons of Tert(High) undifferentiated spermatogonia and Tert(Low) differentiated spermatogonia by RNA sequencing reveals marked differences in cell cycle and key molecular features of each compartment. Transplantation studies show that germline stem cell activity is confined to the Tert(High) cKit(-) population. Telomere shortening in telomerase knockout strains causes depletion of undifferentiated spermatogonia and eventual loss of all germ cells after undifferentiated spermatogonia drop below a critical threshold. These data reveal that high telomerase expression is a fundamental characteristic of germline stem cells, thus explaining the broad dependence on telomerase for germline immortality in metazoans.

Indexed as

Gene Expression Regulation, EnzymologicAdult Stem CellsAnimalsCell DifferentiationEmbryonic Stem CellsFlow CytometryGene Knock-In TechniquesMaleMiceMice, Inbred C57BLPromoter Regions, GeneticSpermatogoniaTelomeraseTelomeraseTert protein, mouseaginggermline stem cellsspermatogenesistelomerasetelomeres

Identifiers

PMID26584619
PMCPMC4691947
OpenAlexW2181156889

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.