Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing

ABSTRACT: Alternative splicing expands the proteome complexity and plays essential roles in tissue development and human diseases. However, how spermatogenesis is regulated by alternative splicing remains largely unknown. Here, using germ cell-specific knockout mouse model, we demonstrate that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. Depletion of Srsf10 in germ cells had little effect on the formation of SSCs but impeded the expansion of progenitor spermatogonia, leading to the failure of spermatogonia differentiation and meiosis initiation. This was evidenced by the decreased expression of progenitor cell markers in bulk RNA-seq, and much less progenitor and differentiating spermatogonia in single-cell RNA-seq data. Furthermore, the expression of genes involved in cell cycle was abnormal in all subtypes of spermatogonia identified in single-cell RNA-seq data. Notably, using isolated spermatogonia, we found that Srsf10 depletion disturbed the alternative splicing of hundreds of genes, which were preferentially associated with cell cycle, mitotic cell cycle checkpoint and germ cell development, including Dazl, Kit, Ret, Sycp1, Nasp and Bora. These data suggest that SRSF10 is critical for the expansion of progenitor spermatogonia by regulating alternative splicing, expanding our understanding of the novel mechanism underlying spermatogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE190646 | GEO | 2022/11/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SRSF2 is required for mRNA splicing and spermatogenesis [LACE-seq]

Project description:Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, is a member of a SRs protein family, which plays significant roles in numerous fundamental biological activities. However, the roles and underlying mechanisms of SRSF2 remain largely unclear during spermatogenesis. Here, we report that SRSF2 is involved in alternative splicing and that male germ cell-specific deletion of Srsf2 by Stra8-GFPCre causes absolute infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 in the male germ cells had harmful influences on the differentiation of spermatogonia and meiosis initiation. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that spermatogenesis, meiotic cell cycle, male gamete generation, reproductive development, and male sex differentiation were involved in the SRSF2 regulatory networks. Furthermore, SRSF2 affects expression and AS of Stra8, Stag3 and Atr in a direct manner, which were critical factors during spermatogenesis. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.

2023-08-18 | GSE206536 | GEO

SRSF2 is required for mRNA splicing and spermatogenesis [RNA-seq]

2023-08-18 | GSE206535 | GEO

SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing

Project description:SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing

| PRJNA787907 | ENA

Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.

Project description:Splicing factor SRSF10 is known to function as a sequence-specific splicing activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Functionally, many of SRSF10-verified alternative exons are linked to pathways of stress and apoptosis. Importantly, reconstituted SRSF10 in knockout cells recovered wild-type splicing patterns and considerably rescued the stress-related defects. Together, our results provide mechanistic insight into SRSF10-regulated alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial role in cell survival under stress conditions. RNA-seq for wide type (WT) and SRSF10-deficient (KO) chicken DT40 cells

2014-01-22 | E-GEOD-53354 | biostudies-arrayexpress

BCAS2 is involved in alternative mRNA splicing in spermatogonia and the transition to meiosis and male fertility

Project description:BCAS2 (Breast cancer amplified sequence 2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we report that BCAS2 is specifically enriched in spermatogonia of mouse testes. Conditional disruption of Bcas2 in male germ cells impairs spermatogenesis and leads to male mouse infertility. Although the spermatogonia appear grossly normal, spermatocytes in meiosis prophase I and meiosis events (recombination and synapsis) are rarely observed in the BCAS2-depleted testis. In BCAS2 null testis, 245 genes are altered in alternative splicing forms; at least three spermatogenesis-related genes (Dazl, Ehmt2 and Hmga1) can be verified. In addition, disruption of Bcas2 results in a significant decrease of the full-length form and an increase of the short form (lacking exon 8) of DAZL protein. Altogether, our results suggest that BCAS2 regulates alternative splicing in spermatogonia and the transition to meiosis initiation, and male fertility.

2016-11-15 | GSE89801 | GEO

Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.

2014-01-22 | GSE53354 | GEO

Expression changes in mRNA expression associated with the effects of nutrition on apoptosis and spermatogenesis in the adult testis

Project description:We tested whether the defects in spermatogenesis and increases in germ cell apoptosis that are induced by under-nutrition are associated with changes in mRNA expression and pre-mRNA alternative splicing in the testis. Groups of 8 male sheep were fed for a 10% increase or 10% decrease in body mass over 65 days. We identified 2,243 mRNAs, including TP53 and Claudin 11, that were differentially expressed in testis from underfed and well-fed sheep (FDR < 0.1), and found that their changes in expression were associated with germ cells, testis size, cell cycle and spermatogenesis variations. Furthermore, pairs of 269 mRNAs and 48 miRNAs were indentified based on target prediction and the negative regulatory effect of miRNAs on mRNA expression with functions involved in abnormal reproductive morphology, apoptosis and male infertility. Nutrition did not affect the total number of alternative splicing junctions, but affected 1,040 alternative splicing events (FDR < 0.05, ∆PSI > 10%). A total of 788 genes, including CREM, MAP2, HIPK3 and TRa2β, were differentially spliced between dietary treatments, with functions related to protein localization, cellular metabolic process, post-translational protein modification and spermatogenesis. In addition, three gene modules were positively correlated with spermatogenesis-related phenotypic traits and negatively related to apoptosis-related phenotypic traits. Among these gene modules, seven (CFLAR, PTPRC, F2R, MAP3K1, EPHA7, APP, BCAP31) were also differentially expressed between nutritional treatments, indicating their potential as markers of spermatogenesis or apoptosis. We conclude that under-nutrition causes changes in mRNAs and pre-mRNA alternative splicing that, at least partly, contribute to disrupted spermatogenesis and increased germ cell apoptosis.

2017-03-08 | GSE68274 | GEO

SRSF10 regulates alternative splicing and is required for adipocyte differentiation.

Project description:During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, RNA-seq analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Skipping of lipin1 exon 7 is controlled by SRSF10-regulated cis-element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin1a mRNA. A series of experiments demonstrated that SRSF10 controls the production of lipin1a and thus promotes adipocyte differentiation. Indeed, lipin1a expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin1 pre-mRNA splicing. RNA-seq for wide type (WT) and SRSF10-deficient (KO) mouse MEF cells

2014-05-12 | E-GEOD-54226 | biostudies-arrayexpress

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase

Project description:DDB1-cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognises and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Our study found that Dcaf2 was highly expressed in the germ cells of human and mouse testes. To determine whether DCAF2 plays a crucial role in spermatogenesis, we generated germ cell conditional Dcaf2 knockout mice by crossing Dcaf2fl/fl mice with Stra8-Cre mice. The depletion of Dcaf2 in germ cells causes a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further study showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG). Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells. Co-overexpression of p21 and TDG exacerbates DNA damage and apoptosis. These results suggest that DCAF2 maintains the expansion and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG.

2024-05-01 | GSE259242 | GEO

SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [LACE-seq]

Project description:Alternative splicing (AS) plays significant roles in fundamental biological activities. AS also are prevalent in the testis, but the regulations of alternative splicing in spermatogenesis is vague. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1), plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility and abnormal spermatogenesis. We further demonstrated that Srsf1 is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 regulatory networks have functions in spermatogenesis. Particularly, we found that SRSF1 affects the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Taken together, our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing.

2024-03-31 | GSE226551 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data