Evidence map›Paper›PMID 19109221›Full record

ArticleBiology of reproduction2009

The molecular signature of spermatogonial stem/progenitor cells in the 6-day-old mouse testis.

Maria Kokkinaki, Tin-Lap Lee, Zuping He, Jiji Jiang, Nady Golestaneh, Marie-Claude Hofmann, Wai-Yee Chan, Martin Dym

Open access · bronzeAbstract read
In one paragraph

Article in Biology of reproduction, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 5% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. The Biology and Regulation of Spermatogonial Stem Cells in the Niche.Advances in experimental medicine and biology · 2025
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. International journal of fertility & sterility · 2020
    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

8 authors at 4 institutions in 1 country.

Maria KokkinakiDepartment of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia 20057, USA.
Tin-Lap Lee
Zuping He
Jiji Jiang
Nady Golestaneh
Marie-Claude Hofmann
Wai-Yee Chan
Martin Dym
Georgetown University · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USGeorgetown University Medical Center · USUniversity of Illinois Urbana-Champaign · US

Funding

FATE OF SPERMATOGONIAL STEM CELLSR01HD033728 · NICHD · GEORGETOWN UNIVERSITY · PI DYM, MARTIN · 1997 to 2007
$2.6M
Transcription regulation and functional studies of germ cell specific genesZIAHD008817 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI RENNERT, OWEN · 2009 to 2013
$2.4M
Isolation and Characterization of Testis Stem CellsR01HD044543 · NICHD · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI HOFMANN, MARIE-CLAUDE CATHERINE · 2005 to 2009
$1.4M
CDA: Isolation and Characterization Testis Stem Cells; Influence of GDNFK02HD054607 · NICHD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HOFMANN, MARIE-CLAUDE CATHERINE · 2007 to 2011
$638k
Intramural NIH HHSNICHD NIH HHS HD012345NICHD NIH HHS HD033728NICHD NIH HHS K02 HD054607NICHD NIH HHS R01 HD044543
6 · The paper itself

Abstract

To characterize the molecular phenotype of spermatogonial stem cells (SSCs), we examined genes that are differentially expressed in the stem/progenitor spermatogonia compared to nonstem spermatogonia. We isolated type A spermatogonia (stem and nonstem type A) from 6-day-old mice using sedimentation velocity at unit gravity and further selected the stem/progenitor cell subpopulation by magnetic activated cell sorting with an antibody to GDNF-receptor-alpha-1 (GFRA1). It has been previously shown that GFRA1 is expressed in SSCs and is required for their stemness. The purity of the isolated cells was approximately 95% to 99% as indicated by immunocytochemistry using anti-GFRA1. Comparison of GFRA1-positive and GFRA1-negative spermatogonia by microarray analysis revealed 99 known genes and 12 uncharacterized transcripts that are overexpressed in the former cell population with a >2-fold change. Interestingly, the highest level of overexpression was observed for Csf1r, encoding the receptor for macrophage colony-stimulating factor (M-CSF, official symbol CSF1), which has a well-established role in the regulation of myeloid progenitor cells. Analysis of our microarray data with a bioinformatics software program (Ingenuity Systems) revealed the potential role of various signaling pathways in stem/progenitor spermatogonia and suggested a common pathway for GFRA1 and CSF1R that may lead to their proliferation. Further investigation to test this hypothesis has shown that CSF1 promotes cell proliferation in primary cultures of the isolated type A spermatogonia and in the spermatogonial-derived stem cell line C18-4. Semiquantitative RT-PCR and immunohistochemistry confirmed the previously mentioned microarray data. Collectively, this study provides novel molecular signatures for stem/progenitor spermatogonia and demonstrates a role for CSF1/CSF1R signaling in regulating their proliferation.

Indexed as

Gene Expression ProfilingAnimalsAnimals, NewbornCell ProliferationCells, CulturedGene Expression Regulation, DevelopmentalGene Regulatory NetworksGlial Cell Line-Derived Neurotrophic Factor ReceptorsMacrophage Colony-Stimulating FactorMaleMiceMice, Inbred BALB CModels, BiologicalOligonucleotide Array Sequence AnalysisReceptor, Macrophage Colony-Stimulating FactorSpermatogenesisGfra1 protein, mouseGlial Cell Line-Derived Neurotrophic Factor ReceptorsMacrophage Colony-Stimulating FactorReceptor, Macrophage Colony-Stimulating Factor

Identifiers

PMID19109221
PMCPMC6322428
OpenAlexW2163078895

What OpenQuestion holds

Textmetadata
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.