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Extracellular vesicles-mediated transfer of let-7b/7c promotes the proliferation of transition-state spermatogonia in neonatal mouse testis [miRNA-seq]

ABSTRACT: The self-renewal and differentiation of spermatogonial stem cells (SSCs) play essential roles in spermatogenesis. Extracellular vesicle (EV) is a universal strategy for intercellular communications in stem cell niches. However, the involvement of EVs in regulating the SSCs remains largely unknown. In this study, we have revealed the role of testis EVs isolated from postnatal day 7 (PND7) neonatal mouse testis in guiding spermatogonia into a transit-amplifying state with increased proliferation while retaining their differentiation potential. We profiled the repertoires of proteins and small RNAs by proteomic and small RNA transcriptomic analyses, respectively. We further showed that the EVs secreted by undifferentiated spermatogonia and the Sertoli cell lines, but not from more differentiated germ cell lines, conveyed let-7b/7c miRNA cargoes to spermatogonia, which mediates the effect of EVs on spermatognial transit amplification. Together, this study has deciphered an important intercellular communication within the spermatogonial niche mediated by let-7b/7c cargoes of EVs, providing a new insight into the regulation of SSCs and spermatogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE308837 | GEO | 2025/09/30

REPOSITORIES: GEO

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Extracellular vesicles-mediated transfer of let-7b/7c promotes the proliferation of transition-state spermatogonia in neonatal mouse testis [scRNA-seq]

Project description:The self-renewal and differentiation of spermatogonial stem cells (SSCs) play essential roles in spermatogenesis. Extracellular vesicle (EV) is a universal strategy for intercellular communications in stem cell niches. However, the involvement of EVs in regulating the SSCs remains largely unknown. In this study, we have revealed the role of testis EVs isolated from postnatal day 7 (PND7) neonatal mouse testis in guiding spermatogonia into a transit-amplifying state with increased proliferation while retaining their differentiation potential. We profiled the repertoires of proteins and small RNAs by proteomic and small RNA transcriptomic analyses, respectively. We further showed that the EVs secreted by undifferentiated spermatogonia and the Sertoli cell lines, but not from more differentiated germ cell lines, conveyed let-7b/7c miRNA cargoes to spermatogonia, which mediates the effect of EVs on spermatognial transit amplification. Together, this study has deciphered an important intercellular communication within the spermatogonial niche mediated by let-7b/7c cargoes of EVs, providing a new insight into the regulation of SSCs and spermatogenesis.

2025-09-30 | GSE308840 | GEO

Testis single-cell RNA-sequencing in the cynomolgus macaque reveals conserved transcriptional profiles during mammalian spermatogenesis

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2020-08-13 | E-MTAB-8979 | biostudies-arrayexpress

The histone demethylase KDM1A is essential for the maintenance and differentiation of spermatogonial stem cells and progenitors

Project description:Little is known of the fundamental processes governed by epigenetic mechanisms in the supplier cells of spermatogenesis, the spermatogonial stem cells (SSCs). The histone H3 lysine demethylase KDM1A is expressed in spermatogonia. We hypothesized that KDM1A serves in transcriptional regulation of SSCs and fertility. Using a conditional deletion of Kdm1a [conditional knockout (cKO)] in mouse spermatogonia, we determined that Kdm1a is essential for spermatogenesis as adult cKO males completely lack germ cells. Analysis of postnatal testis development revealed that undifferentiated and differentiating spermatogonial populations form in Kdm1a-cKO animals, yet the majority fail to enter meiosis. Loss of germ cells in the cKO was rapid with none remaining by postnatal day (PND) 21. To gain insight into the mechanistic implications of Kdm1a ablation, we isolated PND 6 spermatogonia enriched for SSCs and analyzed their transcriptome by RNA sequencing. Loss of Kdm1a was associated with altered transcription of 1206 genes. Importantly, differentially expressed genes between control and Kdm1a-cKO animals included those that are essential for SSC and progenitor maintenance and spermatogonial differentiation. The complete loss of fertility and failure to establish spermatogenesis indicate that Kdm1a is a master controller of gene transcription in spermatogonia and is required for SSC and progenitor maintenance and differentiation.

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The miRNA profiling of goat CD49f-positive and negative testicular cells

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2023-02-24 | PXD037764 | Pride

Cnot3 is required for male germ cell development and spermatogonial stem cell maintenance [RNA-Seq]

Project description:The foundation of spermatogenesis and lifelong fertility is provided by spermatogonial stem cells (SSCs). SSCs divide asymmetrically to either replenish their numbers (self-renewal) or produce undifferentiated progenitors that proliferate before committing to differentiation. However, regulatory mechanisms governing SSC maintenance are poorly understood. Here, we show that the CCR4-NOT mRNA deadenylase complex subunit CNOT3 plays a critical role in sustaining spermatogonial populations in mice. We found that Cnot3 is highly expressed in undifferentiated spermatogonia, and its deletion in spermatogonia resulted in germ cell loss and infertility. Furthermore, it is required for SSC self-renewal based on single cell analyses in vivo and SSC culture in vitro. Mechanistically, Cnot3 deletion led to the de-repression of transcripts encoding factors involved in spermatogonial differentiation, including those in the glutathione redox pathway that are critical for SSC maintenance. Together, our study reveals that CNOT3 – likely via the CCR4-NOT complex – actively degrades transcripts encoding differentiation factors to support the spermatogonial pool and ensure the progression of spermatogenesis, highlighting the importance of CCR4-NOT-mediated post-transcriptional gene regulation during male germ cell development.

2025-07-23 | GSE247288 | GEO

Cnot3 is required for male germ cell development and spermatogonial stem cell maintenance [scRNA-Seq]

2025-07-23 | GSE247287 | GEO

Identification of ID4-interacting proteins in cultured undifferentiated spermatogonia

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2025-05-06 | PXD049346 | Pride

Sertoli Cell-Only Syndrome Human Transcriptome Profiling Study

Project description:<p>Sertoli cell-only syndrome is severe form of human male infertility in which most seminiferous tubules appear to lack all spermatogenic cells, including spermatogonial stem cells (SSCs). However, a few small tubule segments of some patients have active spermatogenesis and, thus, functional stem cell niches and SSCs. Normally SSCs replicate, migrate and refill adjacent empty niches, but this does not appear to occur in SCO syndrome. We hypothesized that this failure occurs because most niches are dysfunctional. As Sertoli cells are essential to formation of these niches, we used RNAseq to compare the transcriptomes of human testes with qualitatively normal (complete) spermatogenesis (n=4) with the transcriptomes of human testes with SCO syndrome (n=7). We then focused our analysis on the expression of transcripts that bioinformatic analyses identified as Sertoli cell signature transcripts. Results show that Sertoli cells in SCO testes express abnormally low levels of GDNF, FGF8 and BMP4, all of which are important regulators of mouse SSCs and/or progenitor spermatogonia. Sertoli cells in SCO testes express significantly reduced levels of transcripts for proteins that polarize the Sertoli cell plasma membrane and regulate the trafficking of cell adhesion and gap junction proteins in and out of that plasma membrane.</p>

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2014-02-27 | E-GEOD-55381 | biostudies-arrayexpress

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