Meiotic cohesin RAD21L shapes 3D genome structure and transcription in the male germline [scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1265245 | ENA |
REPOSITORIES: ENA
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Project description:Meiotic cohesin RAD21L shapes 3D genome structure and transcription in the male germline [HiC]
| PRJNA1265250 | ENA
Project description:The unique genome organization that chromosome acquired during meiosis is essential for fertility. Yet, the functional implications of the fine-scale spatial 3D genome folding during this process remain poorly understood. Here, we study the impact of RAD21L depletion, a meiosis-specific cohesin subunit, on the 3D genome architecture and gene expression in the male germ line. Employing fluorescence activated cell sorting, chromosome conformation capture and single cell RNA-seq, we found that the absence of RAD21L impairs chromatin organization during meiosis, leading to pronounced alterations of genome compartmentalization and inter- and intra-chromosomal interactions. This conspicuous genome remodelling also disrupts bouquet formation, resulting in increased telomeric interactions between heterologous chromosomes in primary spermatocytes. Importantly, genome remodelling was accompanied by detectable transcriptional dysregulation in spermatogonia and primary spermatocytes, mainly affecting sex chromosomes. Overall, we demonstrate how cohesin shapes the 3D genome reorganization genome-wide during spermatogenesis and influences its transcriptional landscape.
2025-09-01 | GSE297600 | GEO
Project description:The unique genome organization that chromosome acquired during meiosis is essential for fertility. Yet, the functional implications of the fine-scale spatial 3D genome folding during this process remain poorly understood. Here, we study the impact of RAD21L depletion, a meiosis-specific cohesin subunit, on the 3D genome architecture and gene expression in the male germ line. Employing fluorescence activated cell sorting, chromosome conformation capture and single cell RNA-seq, we found that the absence of RAD21L impairs chromatin organization during meiosis, leading to pronounced alterations of genome compartmentalization and inter- and intra-chromosomal interactions. This conspicuous genome remodelling also disrupts bouquet formation, resulting in increased telomeric interactions between heterologous chromosomes in primary spermatocytes. Importantly, genome remodelling was accompanied by detectable transcriptional dysregulation in spermatogonia and primary spermatocytes, mainly affecting sex chromosomes. Overall, we demonstrate how cohesin shapes the 3D genome reorganization genome-wide during spermatogenesis and influences its transcriptional landscape.
2025-09-01 | GSE297601 | GEO
Project description:The mitotic STAG3–cohesin complex shapes male germline nucleome
| PRJNA1020801 | ENA
Project description:Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells (SSCs) which constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown. Here, we show that STAG3, this far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice. Due to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs), rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome. Moreover, in the absence of STAG3–cohesin, SSCs show an impaired differentiation priming for spermatogenesis. Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation. Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.
2025-07-07 | GSE243961 | GEO
Project description:Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells (SSCs) which constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown. Here, we show that STAG3, this far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice. Due to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs), rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome. Moreover, in the absence of STAG3–cohesin, SSCs show an impaired differentiation priming for spermatogenesis. Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation. Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.
2025-07-07 | GSE243960 | GEO
Project description:Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells (SSCs) which constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown. Here, we show that STAG3, this far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice. Due to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs), rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome. Moreover, in the absence of STAG3–cohesin, SSCs show an impaired differentiation priming for spermatogenesis. Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation. Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.
2025-07-07 | GSE243959 | GEO
Project description:Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells (SSCs) which constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown. Here, we show that STAG3, this far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice. Due to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs), rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome. Moreover, in the absence of STAG3–cohesin, SSCs show an impaired differentiation priming for spermatogenesis. Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation. Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.
2025-07-07 | GSE243958 | GEO
Project description:Cohesin is a tetrameric protein complex with a ring-like structure that entraps DNA to ensure sister chromatid cohesion and higher-order chromatin organization. The mechanism by which cohesin regulates chromatin structure and gene expression remains a fundamental question. In multicellular organisms, germ cells are unique in that they tailor chromatin organization toward generating totipotency. As part of this program, spermatogonial stem cells (SSCs) in mammals, the source for male gametes, acquire distinctive chromatin organization with exceptionally weak insulation, but the underlying mechanism is unknown. Here, we show that STAG3, exclusively known to form meiotic cohesins, contributes to a mitotic cohesin defining nucleome programming during male germline development. With slower loop extrusion and shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs) demarcated by CCCTC-binding factor (CTCF), re-wires both enhancer–promoter and Polycomb-mediated repressive interactions, and creates finer and strengthened compartments, establishing a characteristic SSC nucleome. Moreover, STAG3–cohesin controls the balance between SSC self-renewal and differentiation for spermatogenesis. Notably, mitotic STAG3–cohesin is also highly expressed in human B cells and potentially involved in B-cell malignancies. Thus, mitotic STAG3–cohesin with its unique loop extrusion property elucidates a principle for male germline nucleome programming and, more broadly, may contribute to human malignancy.
2025-07-07 | PXD045854 | JPOST Repository
Project description:Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells (SSCs) which constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown. Here, we show that STAG3, this far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice. Due to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs), rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome. Moreover, in the absence of STAG3–cohesin, SSCs show an impaired differentiation priming for spermatogenesis. Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation. Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.
2025-07-07 | GSE274225 | GEO