ArticleOncotarget2015
Loss of Gata4 in Sertoli cells impairs the spermatogonial stem cell niche and causes germ cell exhaustion by attenuating chemokine signaling.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 72 citations in OpenAlex.
- Molecular mechanisms and translational implications in apoptosis, ferroptosis, pyroptosis, and cuproptosis of spermatogonial stem cells.Cellular and molecular life sciences : CMLS · 2026Review
- Concomitant Effect of Hypothyroidism with Obesity on Testicular and Sperm Function in Male ICR Mice: Involvement of TGFβ/SMAD Signaling.Cell biochemistry and biophysics · 2026Article
- Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis.Reproductive biology and endocrinology : RB&E · 2023Article
- Do macrophages play a role in the adverse effects of endocrine disrupting chemicals (EDCs) on testicular functions?Frontiers in toxicology · 2023Review
- Centrosome linker protein C-Nap1 maintains stem cells in mouse testes.EMBO reports · 2022Article
- Sertoli Cell-Germ Cell Interactions Within the Niche: Paracrine and Juxtacrine Molecular Communications.Frontiers in endocrinology · 2022Review
- Insights Into the Roles of GATA Factors in Mammalian Testis Development and the Control of Fetal Testis Gene Expression.Frontiers in endocrinology · 2022Review
- Organotypic Rat Testicular Organoids for the Study of Testicular Maturation and Toxicology.Frontiers in endocrinology · 2022Article
- Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function.PLoS genetics · 2021Article
- Mediterranean Pine Vole,Animals : an open access journal from MDPI · 2021Article
- Etomoxir regulates the differentiation of male germ cells by specifically reducing H3K27ac level.BMC developmental biology · 2021Article
- UXT in Sertoli cells is required for blood-testis barrier integrity†.Biology of reproduction · 2020Article
- Cyclin A2 is essential for mouse gonocyte maturation.Cell cycle (Georgetown, Tex.) · 2020Article
- Differential Regulation ofCells · 2019Article
- Formation of organotypic testicular organoids in microwell culture†.Biology of reproduction · 2019Article
- Testicular germ cell tumor: a comprehensive review.Cellular and molecular life sciences : CMLS · 2019Review
- Steroidogenic Factor 1 (Nr5a1) is Required for Sertoli Cell Survival Post Sex Determination.Scientific reports · 2019Article
- Germline deletion of Cdyl causes teratozoospermia and progressive infertility in male mice.Cell death & disease · 2019Article
- Fibroblast growth factor-5 promotes spermatogonial stem cell proliferation via ERK and AKT activation.Stem cell research & therapy · 2019Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sertoli cells, the primary somatic cell in the seminiferous epithelium, provide the spermatogonial stem cell (SSC) microenvironment (niche) through physical support and the expression of paracrine factors. However, the regulatory mechanisms within the SSC niche, which is primarily controlled by Sertoli cells, remain largely unknown. GATA4 is a Sertoli cell marker, involved in genital ridge initiation, sex determination and differentiation during the embryonic stage. Here, we showed that neonatal mice with a targeted disruption of Gata4 in Sertoli cells (Gata4(flox/flox); Amh-Cre; hereafter termed Gata4 cKO) displayed a loss of the establishment and maintenance of the SSC pool and apoptosis of both gonocyte-derived differentiating spermatogonia and meiotic spermatocytes. Thus, progressive germ cell depletion and a Sertoli-cell-only syndrome were observed as early as the first wave of murine spermatogenesis. Transplantation of germ cells from postnatal day 5 (P5) Gata4 cKO mice into Kit(W/W-v) recipient seminiferous tubules restored spermatogenesis. In addition, microarray analyses of P5 Gata4 cKO mouse testes showed alterations in chemokine signaling factors, including Cxcl12, Ccl3, Cxcr4 (CXCL12 receptor), Ccr1 (CCL3 receptor), Ccl9, Xcl1 and Ccrl2. Deletion of Gata4 in Sertoli cells markedly attenuated Sertoli cell chemotaxis, which guides SSCs or prospermatogonia to the stem cell niche. Finally, we showed that GATA4 transcriptionally regulated Cxcl12 and Ccl9, and the addition of CXCL12 and CCL9 to an in vitro testis tissue culture system increased the number of PLZF+ undifferentiated spermatogonia within Gata4 cKO testes. Together, these results reveal a novel role for GATA4 in controlling the SSC niche via the transcriptional regulation of chemokine signaling shortly after birth.
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