Induction of meiosis from human pluripotent stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE268385 | GEO | 2024/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:The meiosis-specific chromosomal events of homolog pairing, synapsis, and recombination occur over an extended meiotic prophase I. In this study, we show that, in mice, maintenance of an extended meiotic prophase I requires the gene Meioc, a germ-cell specific factor conserved in most metazoans. Using immunoprecipitation and quantitative mass spectrometry, we identify proteins that interact with MEIOC in the mouse germ line.
2017-03-27 | PXD005473 | Pride
Project description:Repro9 in an allele of Mybl1 (A-Myb) transcription factor obtained in ENU screen to identify alleles causing mouse infertility. Repro9/repro9 mutant males are infertile due to meiotic arrest at pachytene stage. Mutants show wide range of abnormalities including inefficient chromosome synapsis, sex body formation and progression through meiotic cycle. Females are unaffected. To determine genes transcriptionally regulated by MYBL1 we analyzed gene expression profiles of wild type and repro9/repro9 mutant testis at 14 and 17 days postpartum. Analysis revealed many misregulated genes, in majority downregulated, at day 14 pp and even more at day 17 pp, probably due to secondary effects of meiotic arrest. Significantly misregulated genes were characterized by Gene Ontology. Comparative gene expression analysis uncovered potential targets of MYBL1 regulation that play roles in regulation of transcription, cell cycle, apoptosis, protein phosphorylation and ubiquitination, chromosome organization and others. Abstract:The transcriptional regulation of mammalian meiosis is poorly characterized, due to few genetic and ex vivo models. From a genetic screen, we identify the transcription factor MYBL1 as a male-specific master regulator of several critical meiotic processes. Spermatocytes bearing a novel separation-of-function allele (Mybl1repro9) had subtle defects in autosome synapsis in pachynema, a high incidence of unsynapsed sex chromosomes, incomplete double strand break (DSB) repair on synapsed pachytene chromosomes, and a lack of crossing-over. MYBL1 protein appears in pachynema, and its mutation caused specific alterations in expression of diverse genes, including some translated postmeiotically. These data, coupled with chromatin immunoprecipitation (ChIP-chip) experiments and bioinformatic analysis of promoters, identified direct targets of MYBL1 regulation. Meiosis in mutant females appears unaffected. These results reveal that MYBL1 is a master regulator of meiotic genes that are involved in multiple processes in spermatocytes, including chromosome synapsis, recombination, and cell cycle progression through pachynema. RNA was extracted from wt and repro9/repro9 mutant testis from 14 and 17 days old mice. This two time points were selected for sample enrichment in early/midpachytene and latepachytene/diplotene spermatocytes, respectively. Total testis RNA from wild-type (≥3) and mutant (≥3) mice was reverse-transcribed into double stranded cDNA, and biotin-labeled cRNA (GeneChip IVT labeling kit, Affymetrix, Santa Clara, CA) was hybridized to Affymetrix mouse genome 430 2.0 GeneChips containing. The raw data was processed using Affymetrix GCOS software. Two-way ANOVA analysis resolved differentially expressed (DE) genes either between genotypes and/or days using MeV(version 4.6.1) on log2-transformed expression values. Results were multiple test corrected with the Benjamini-Hochberg method to control the false discovery rate (FDR) in R. ~800 genes significant at FDR<=0.025 were selected as differentially expressed for downstream analysis.
2011-10-18 | E-GEOD-28025 | biostudies-arrayexpress
Project description:Repro9 in an allele of Mybl1 (A-Myb) transcription factor obtained in ENU screen to identify alleles causing mouse infertility. Repro9/repro9 mutant males are infertile due to meiotic arrest at pachytene stage. Mutants show wide range of abnormalities including inefficient chromosome synapsis, sex body formation and progression through meiotic cycle. Females are unaffected. To determine genes transcriptionally regulated by MYBL1 we analyzed gene expression profiles of wild type and repro9/repro9 mutant testis at 14 and 17 days postpartum. Analysis revealed many misregulated genes, in majority downregulated, at day 14 pp and even more at day 17 pp, probably due to secondary effects of meiotic arrest. Significantly misregulated genes were characterized by Gene Ontology. Comparative gene expression analysis uncovered potential targets of MYBL1 regulation that play roles in regulation of transcription, cell cycle, apoptosis, protein phosphorylation and ubiquitination, chromosome organization and others. Abstract:The transcriptional regulation of mammalian meiosis is poorly characterized, due to few genetic and ex vivo models. From a genetic screen, we identify the transcription factor MYBL1 as a male-specific master regulator of several critical meiotic processes. Spermatocytes bearing a novel separation-of-function allele (Mybl1repro9) had subtle defects in autosome synapsis in pachynema, a high incidence of unsynapsed sex chromosomes, incomplete double strand break (DSB) repair on synapsed pachytene chromosomes, and a lack of crossing-over. MYBL1 protein appears in pachynema, and its mutation caused specific alterations in expression of diverse genes, including some translated postmeiotically. These data, coupled with chromatin immunoprecipitation (ChIP-chip) experiments and bioinformatic analysis of promoters, identified direct targets of MYBL1 regulation. Meiosis in mutant females appears unaffected. These results reveal that MYBL1 is a master regulator of meiotic genes that are involved in multiple processes in spermatocytes, including chromosome synapsis, recombination, and cell cycle progression through pachynema.
2011-10-19 | GSE28025 | GEO
Project description:Homologous pairing and synapsis are essential in meiotic prophase I during spermatogenesis. However, the underlying mechanisms of how alternative splicing (AS) functions in homologous pairing and synapsis remain largely unclear. We reveal that SRSF1 is essential for gene expression and AS in homologous pairing and synapsis. Conditional knockout (cKO) of Srsf1 in mouse germ cells impaired homologous pairing and synapsis, leading to non-obstructive azoospermia (NOA). SRSF1 was required for initial homology recognition, telomere-led chromosome movement, and synaptonemal complex (SC) assembly. Moreover, SRSF1 interacted with TRA2B and U2AF2, directly binding and regulating the expression of Dmc1, Sycp1, Sun1, and Majin via AS to implement homologous pairing and synapsis during the meiotic prophase I program. Altogether, our data reveal the critical role of an SRSF1-mediated post-transcriptional regulatory mechanism in homologous pairing and synapsis during meiotic prophase I, providing a framework for elucidating the molecular mechanisms underlying the post-transcriptional network of male meiosis.
2024-01-09 | GSE227403 | GEO
Project description:Homologous pairing and synapsis are essential in meiotic prophase I during spermatogenesis. However, the underlying mechanisms of how alternative splicing (AS) functions in homologous pairing and synapsis remain largely unclear. We reveal that SRSF1 is essential for gene expression and AS in homologous pairing and synapsis. Conditional knockout (cKO) of Srsf1 in mouse germ cells impaired homologous pairing and synapsis, leading to non-obstructive azoospermia (NOA). SRSF1 was required for initial homology recognition, telomere-led chromosome movement, and synaptonemal complex (SC) assembly. Moreover, SRSF1 interacted with TRA2B and U2AF2, directly binding and regulating the expression of Dmc1, Sycp1, Sun1, and Majin via AS to implement homologous pairing and synapsis during the meiotic prophase I program. Altogether, our data reveal the critical role of an SRSF1-mediated post-transcriptional regulatory mechanism in homologous pairing and synapsis during meiotic prophase I, providing a framework for elucidating the molecular mechanisms underlying the post-transcriptional network of male meiosis.
2024-01-08 | GSE227303 | GEO
Project description:Faithful meiotic chromosome inheritance and fertility relies on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs on chromosomes that have successfully initiated crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 Kb near all telomeres that escape DSB downregulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes. Grant ID: Research grant #6-FY16-208 Grant title: Meiotic segregation of small chromosomes Funding Source: March of Dimes Foundation Affiliation: NEW YORK UNIVERSITY Name: Andreas Hochwagen
2019-01-10 | GSE105111 | GEO
Project description:The pachynema progression, a crucial meiotic process, contributes to the completion of prophase I. Nevertheless, the regulation of this significant meiotic process remains poorly understood. In this study, we identified a novel testis-specific protein HSF5, which regulates pachynema progression during male meiosis in a chromatin-binding manner. Deficiency of HSF5 results in meiotic arrest and male infertility, characterized as unconventionally accumulated pachynema halting at the mid-to-late stage, with extensive spermatocyte apoptosis. Our scRNA-seq data confirmed consistent expressional alterations of certain driver genes(Sycp1, Msh4, Meiob, etc.) crucial for pachynema progression in Hsf5-/- individuals. Ulteriorly, HSF5 was revealed to primarily bind to promoter regions of such key divers by CUT&Tag analysis. Also, our results demonstrated that HSF5 biologically interacted with the chromatin-remodeling SWI/SNF complex, and it could function as a transcriptional factor for pachynema progression during meiosis. Therefore, our study underscored the importance of the chromatin-associated HSF5 for the differentiation of spermatocytes, improving the protein regulatory network of the pachynema progression.
2024-08-23 | PXD053613 | Pride
Project description:Meiosis creates genetic diversity by recombination and segregation of chromosomes. The synaptonemal complex assembles during meiotic prophase I and assists faithful exchanges between homologous chromosomes, but how its assembly/disassembly is regulated remains to be understood. Here we report how two major post-translational modifications, phosphorylation and ubiquitination, co-operate to promote synaptonemal complex assembly. We found that the ubiquitin ligase complex SCF is important for assembly and maintenance of the synaptonemal complex in Drosophila female meiosis. This function of SCF is mediated by two substrate-recognising F-box proteins, Slmb/βTrcp and Fbxo42. SCF-Fbxo42 downregulates the phosphatase subunit PP2A-B56, which is important for synaptonemal complex assembly and maintenance.
2020-12-07 | PXD022755 | Pride
Project description:Meiosis is a specialized division that is specifically engaged in germ cells. This program is finely and dichotomically regulated: germ cells enter meiosis at fetal life in ovaries (13.5 dpc) and only at post-natal life in testes (8 dpp). We used microarrays to determine the gene expression modifications in Meioc mutant gonads displaying early meiotic defects. 14.5 dpc ovaries and 8 dpp testes from Meioc+/+ and Meioc-/- mice (NMRI) were dissected and processed for RNA extraction and hybridization on Affymetrix microarrays. Two pools were analysed for each genotype and each sex. We sought to constitutes pairs (A and B) of wild type and knock-out pools from embryos and pups that were homogenous for developmental stages and from matched littermates. 10 ovaries from 5 embryos composed each pool for females and 4 testes from 4 pups composed each pool for males.
2015-11-19 | E-GEOD-66880 | biostudies-arrayexpress
Project description:Chromosome movements and programmed DNA double-strand breaks (DSBs) promote homologue pairing and initiate recombination at meiosis onset. Checkpoints implement termination of these events when all chromosomes achieve synapsis and form crossover precursors, ensuring meiotic progression. We show that termination of chromosome movement and DSB formation is reversible and is continuously implemented by the synaptonemal complex (SC), which silences chromosome signals that promote CHK-2 activity. Forced removal of the SC or different meiosis-specific cohesin complexes, which are individually required for SC stability, causes rapid CHK-2-dependent reinstallation of the DSB-formation and chromosome-movement machinery. This nuclear reorganization occurs without transcriptional changes, but requires signalling from HORMA protein HTP-1. Conversely, CHK-2 inactivation causes rapid disassembly of the DSB-formation and chromosome-movement machinery. Thus, nuclear organization is constantly controlled by the level of CHK-2 activity. Our results uncover an unexpected plasticity of the meiotic program and show how chromosome signalling integrates nuclear organization with meiotic progression.
2020-06-17 | GSE134989 | GEO