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CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice

ABSTRACT: CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice

PROVIDER: PRJNA794370 | ENA |

REPOSITORIES: ENA

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CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice [CUT&TAG]

Project description:Male spermatogenesis is sustained by homeostatic balance between the self-renewal and differentiation of spermatogonial stem cells (SSCs), which is dependent on the strict regulation of transcriptional factor and chromatin modulator gene expression. Chromodomain helicase DNA-binding protein 4 (CHD4) is highly expressed in SSCs but roles in mouse spermatogenesis are unexplored. Here, we report that the germ-cell-specific deletion of Chd4 resulted in complete infertility in male mice, with rapid loss of SSCs and excessive germ cell apoptosis. Chd4-knockdown in cultured SSCs also promoted the expression of apoptosis-related genes and thereby activated the tumor necrosis factor signaling pathway. Mechanistically, CHD4 occupies the genomic regulatory region of key apoptosis-related genes including Jun and Nfkb1. Together, our findings reveal the determinant role of CHD4 in SSCs survival in vivo, which will offer insight into the pathogenesis of male sterility and potential novel therapeutic targets.

2022-01-08 | GSE193070 | GEO

CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice [RNA-Seq]

2022-01-08 | GSE193069 | GEO

CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice [CUT&TAG]

Project description:CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice [CUT&TAG]

| PRJNA794365 | ENA

CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice [RNA-Seq]

Project description:CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice [RNA-Seq]

| PRJNA794366 | ENA

A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool

Project description:Maintenance and self-renewal of the spermatogonial stem cell (SSC) population is the cornerstone of male fertility. In this manuscript we have identified a key role for the nucleosome remodelling protein Chromodomain Helicase DNA binding protein 4 (CHD4) in regulating SSC function. Gene expression analyses revealed that CHD4 expression is largely restricted to spermatogonia in the mouse testis, and is particularly enriched in SSCs. Using spermatogonial transplantation techniques and RNAi mediated knockdown it was established that loss of Chd4 expression significantly impairs SSC regenerative capacity, resulting in a ~50% reduction in colonisation of recipient testes. A single cell RNA-seq comparison depicted reduced expression of ‘self-renewal’ genes such as Gfra1 and Pten following Chd4 knockdown, along with increased expression of signature progenitor genes, Neurog3 and Dazl. Co-immunoprecipitation analyses demonstrated that CHD4 regulates gene expression in spermatogonia not only though its traditional association with the remodelling complex NuRD, but also via interaction with the GDNF-responsive transcription factor SALL4. Cumulatively, the results of this study depict a previously unappreciated fundamental role for CHD4 in controlling fate decisions in the spermatogonial pool.

2021-06-17 | PXD022066 | Pride

A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool

Project description:To understand the role of the nucleosome remodelling protein CHD4 in regulating spermatogonial stem cell function, we performed single cell RNA-sequencing on undifferentiated spermatogonia from primary culture that had been transfected with either control (non-targeting) siRNA or Chd4 siRNA. Transcriptome profiling revealed reduced expression of ‘self-renewal’ genes following Chd4 knockdown, along with increased expression of signature progenitor genes. Overall, CHD4 was demonstrated to primarily act as an activator of gene expression in SSCs. In pairing these data with additional analyses, including use of an Id4-eGfp transgenic mouse line, spermatogonial transplantation, and co-immunoprecipitation experiments: the findings of our study demonstrated a previously unappreciated and fundamental role for CHD4 in controlling fate decisions in the spermatogonial pool.

2021-05-06 | GSE163027 | GEO

CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-08 | GSE193071 | GEO

RNA Helicase DDX5 Acts as a Critical Regulator for Gonocyte Survival in Neonatal Mouse

Project description:Mammalian spermatogenesis is a dynamic and highly coordinated biological process. The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from their precursor cells, the gonocytes. In this study, we found that Ddx5 is highly expressed in male germ cells from embryonic period. We generated germ-cell-specific Ddx5 knockout mice (Ddx5 cKO) by using Mvh-Cre transgenic mice. Ddx5 homozygous knockout mice resulted in significant smaller size and light weight of testes, but Ddx5 heterzygous knockout mice have no effect on reproduction. Furthermore, Ddx5 homozygous knockout resulted in gradual loss of germ cells in neonate’s testes and a complete loss of germ cells within 6 days after birth, leading to azoospermia and infertility in male adults. Single cell RNA sequencing (scRNA-seq) experiments showed that the expression of genes that are involved in cell cycle and GDNF pathway were significantly decreased in gonocytes after Ddx5 knockout. Together, these results reveal critical functions of Ddx5 in the survival and cell fate determination of gonocytes.

2021-03-21 | GSE158285 | GEO

RNA Helicase DDX5 Acts as a Critical Regulator for Gonocyte Survival in Neonatal Mouse

Project description:RNA Helicase DDX5 Acts as a Critical Regulator for Gonocyte Survival in Neonatal Mouse

| PRJNA664750 | ENA

A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool

Project description:A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool

| PRJNA684464 | ENA