Evidence map›Paper›PMID 33636117›Full record

ArticleStem cell reports2021

Spermatogonial Stem Cell Numbers Are Reduced by Transient Inhibition of GDNF Signaling but Restored by Self-Renewing Replication when Signaling Resumes.

Nicole Parker, Andrew Laychur, Meena Sukwani, Kyle E Orwig, Jon M Oatley, Chao Zhang, Florentine U Rutaganira, Kevan Shokat, William W Wright

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

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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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

9 authors at 6 institutions in 1 country.

Nicole ParkerDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Andrew LaychurDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Meena SukwaniDepartment of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
Kyle E OrwigDepartment of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
Jon M OatleySchool of Molecular Biosciences, Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman WA 99164, USA.
Chao ZhangDepartment of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California San Francisco, 600 16(th) Street, MC 2280, San Francisco, CA 94158, USA.
Florentine U RutaganiraDepartment of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California San Francisco, 600 16(th) Street, MC 2280, San Francisco, CA 94158, USA.
Kevan ShokatDepartment of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California San Francisco, 600 16(th) Street, MC 2280, San Francisco, CA 94158, USA.
William W WrightDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: wwright1@jhu.edu.
Johns Hopkins University · USUniversity of California, San Francisco · USHoward Hughes Medical Institute · USMagee-Womens Research Institute · USUniversity of Pittsburgh · USWashington State University · US

Funding

Small RNA Pathways in Mammalian GametogenesisP50HD076210 · NICHD · CORNELL UNIVERSITY · PI COHEN, PAULA ELAINE · 2014 to 2018
$7.4M
Regulation of Stem Spermatogonia in the Mature TestisR01HD074542 · NICHD · JOHNS HOPKINS UNIVERSITY · PI WRIGHT, WILLIAM WALLACE · 2014 to 2016
$1.2M
NICHD NIH HHS P50 HD076210NICHD NIH HHS R01 HD074542
6 · The paper itself

Abstract

One cause of human male infertility is a scarcity of spermatogonial stem cells (SSCs) in testes with Sertoli cells that neither produce adequate amounts of GDNF nor form the Sertoli-Sertoli junctions that form the blood-testis barrier (BTB). These patients raise the issue of whether a pool of SSCs, depleted due to inadequate GDNF stimulation, will expand if normal signaling is restored. Here, we reduce adult mouse SSC numbers by 90% using a chemical-genetic approach that reversibly inhibits GDNF signaling. Signal resumption causes all remaining SSCs to replicate immediately, but they primarily form differentiating progenitor spermatogonia. Subsequently, self-renewing replication restores SSC numbers. Testicular GDNF levels are not increased during restoration. However, SSC replication decreases as numbers of SSCs and progenitors increase, suggesting important regulatory interactions among these cells. Finally, sequential loss of SSCs and then pachytene spermatocytes causes dissolution of the BTB, thereby recapitulating another important characteristic of some infertile men.

Indexed as

Cell Self RenewalSignal TransductionAdult Germline Stem CellsAnimalsCell CountCell DifferentiationGlial Cell Line-Derived Neurotrophic FactorGlial Cell Line-Derived Neurotrophic Factor ReceptorsInfertility, MaleMaleMiceMice, Inbred C57BLSertoli CellsStem Cell TransplantationGfra1 protein, mouseGlial Cell Line-Derived Neurotrophic FactorGlial Cell Line-Derived Neurotrophic Factor Receptorsblood-testis barrierGDNFGFRα1infertilityprogenitor spermatogoniaRetSertoli cellspermatogonial stem cell

Identifiers

PMID33636117
PMCPMC7940257
OpenAlexW3131246391

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.