Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [CUT&Tag]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE273307 | GEO | 2024/09/27
REPOSITORIES: GEO
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Project description:To understand the functional role of CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, in establishing chromatin states in the formation and maintenance of ovarian reserve and the maintenance of female and male germ cells, we eliminated CHD4 function in germ cells using Ddx4-Cre and Gdf9-iCre to generate CHD4 conditional knockout (Chd4 DcKO and GcKO) mice. We discover that CHD4 defines the chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of female and male germ cells. We then performed ATAC-seq in Chd4 Dctrl and Chd4 DcKO non-growing oocytes and undifferentiated spermatogonia.
2024-09-27 | GSE273308 | GEO
Project description:To understand the functional role of CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, in establishing chromatin states in the formation and maintenance of ovarian reserve and the maintenance of female and male germ cells, we eliminated CHD4 function in germ cells using Ddx4-Cre and Gdf9-iCre to generate CHD4 conditional knockout (Chd4 DcKO and GcKO) mice. We discover that CHD4 defines the chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of female and male germ cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of Chd4 Dctrl and Chd4 DcKO non-growing oocytes and undifferentiated spermatogonia, and Chd4 Gctrl and Chd4 GcKO non-growing and growing oocytes.
2024-09-27 | GSE273306 | GEO
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility. Total RNA, including miRNAs, were purified from a total of six individual mouse samples. The tissue collected was obtained from wild-type (control; n=3) and Dicer1 germ cell knockout (mutant; n=3) testes on P18.
2012-09-10 | E-GEOD-38891 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility. Total RNA, including miRNAs, were purified from a total of six individual mouse samples. The tissue collected was obtained from wild-type (control; n=3) and Dicer1 germ cell knockout (mutant; n=3) testes on P18. One miRNA GCKO sample, M36, was determined to be of poor quality and was excluded from the study; thus, a total of five miRNA samples were analyzed.
2012-09-10 | E-GEOD-38895 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility.
2012-09-10 | GSE38895 | GEO
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility.
2012-09-10 | GSE38891 | GEO
Project description:Cancer cells undergo major epigenetic alterations and transcriptome changes, including ectopic expression of many tissue- and cell type-specific genes. Here we show that the germline-specific RNA helicase DDX4 forms germ granule-like cytoplasmic ribonucleoprotein (RNP) granules in various human and mouse tumors, but not in cultured cancer cells. The DDX4-compexes in tumors contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptome imbalance and affects the alternative splicing landscape of a large number of genes with reported functions in cancer growth and invasiveness, leading to their compromised capability to form xenograft tumors. Importantly, high expression of DDX4-positive granules is associated with poor survival in patients with squamous cell carcinoma of the head and neck, as well as with the histological grade of prostate cancer. Taken together, these results show that the formation of germ granule-resembling DDX4 granules have prognostic value, and they are involved in transcriptome control in cancer cells to promote malignant properties.
2024-06-10 | PXD044856 | Pride
Project description:A method for the long-term maintenance of germ-free flies was established using aseptic isolators. The methodology effectively and reliably yields large numbers of germ-free flies in homogeneous cultures. Germ-free flies exhibited increased lifespan (only female flies) and decreased egg production, markedly reduced fat storage, less midday sleep, and enhanced aggressiveness (male flies). Fructilactobacillus—a species of fly intestinal microbes—was re-colonized in germ-free flies, and these gnotobiotic flies were successfully maintained for numerous generations. The proteome of those flies were analyzed.
2024-10-02 | PXD045847 | JPOST Repository
Project description:People are exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP), via inhalation of particulate matter air pollution and ingestion of grilled and smoked foods. Prenatal exposure to BaP destroys germ cells in ovaries, causing earlier onset of ovarian senescence post-natally. Developing testes are affected at higher doses than ovaries. However, it is not known if adverse effects are transmitted to subsequent generations. We orally dosed pregnant female mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5-11.5 (F1 offspring) or E6.5-15.5 (F2 and F3). Ovarian germ cell and follicle numbers were significantly decreased in F3 females at all doses of BaP; testicular germ cells were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Our study demonstrated that F0 BaP exposure partially disrupted sexual identity of female germ cells transgenerationally.
2023-06-07 | GSE213946 | GEO
Project description:People are exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP), via inhalation of particulate matter air pollution and ingestion of grilled and smoked foods. Prenatal exposure to BaP destroys germ cells in ovaries, causing earlier onset of ovarian senescence post-natally. Developing testes are affected at higher doses than ovaries. However, it is not known if adverse effects are transmitted to subsequent generations. We orally dosed pregnant female mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5-11.5 (F1 offspring) or E6.5-15.5 (F2 and F3). Ovarian germ cell and follicle numbers were significantly decreased in F3 females at all doses of BaP; testicular germ cells were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Our study demonstrated that F0 BaP exposure partially disrupted sexual identity of female germ cells transgenerationally.
2023-06-07 | GSE213945 | GEO