Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis
Abstract Cellular decision-making and tissue homeostasis are governed by transcriptional networks shaped by chromatin accessibility. Using single-nucleus multi-omics, we jointly profile gene expression and chromatin accessibility in 10,335 cells from the Drosophila testis apical tip. This enables in...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62046-9 |
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| author | Patrick van Nierop y Sanchez Pallavi Santhi Sekhar Kerem Yildirim Tim Lange Laura Zoe Kreplin Vigneshwarr Muruga Boopathy Stephanie Rosswag de Souza Kim Dammer David Ibberson Qian Wang Katrin Domsch Anniek Stokkermans Shubhanshu Pandey Petra Kaspar Rafael Martinez-Gallegos Xuefan Gao Aakriti Singh Natalja Engel Fillip Port Michael Boutros Josephine Bageritz Ingrid Lohmann |
| author_facet | Patrick van Nierop y Sanchez Pallavi Santhi Sekhar Kerem Yildirim Tim Lange Laura Zoe Kreplin Vigneshwarr Muruga Boopathy Stephanie Rosswag de Souza Kim Dammer David Ibberson Qian Wang Katrin Domsch Anniek Stokkermans Shubhanshu Pandey Petra Kaspar Rafael Martinez-Gallegos Xuefan Gao Aakriti Singh Natalja Engel Fillip Port Michael Boutros Josephine Bageritz Ingrid Lohmann |
| author_sort | Patrick van Nierop y Sanchez |
| collection | DOAJ |
| description | Abstract Cellular decision-making and tissue homeostasis are governed by transcriptional networks shaped by chromatin accessibility. Using single-nucleus multi-omics, we jointly profile gene expression and chromatin accessibility in 10,335 cells from the Drosophila testis apical tip. This enables inference of 147 cell type-specific enhancer-gene regulons using SCENIC + . We functionally validate key transcription factors, including ovo and klumpfuss, known from other stem cell systems but not previously linked to spermatogenesis. CRISPR-mediated knockout reveals their essential roles in germline stem cell regulation, and we provide evidence that they co-regulate shared targets through overlapping enhancer elements. We further uncover a critical role for canonical Wnt signaling, with Pangolin/Tcf activating lineage-specific targets in the germline, soma, and niche. The Pan eRegulon links Wnt activity to cell adhesion, intercellular signaling and germline stem cell maintenance. Together, our study defines the enhancer-driven regulatory landscape of early spermatogenesis and reveals conserved, combinatorial mechanisms of niche-dependent stem cell control. |
| format | Article |
| id | doaj-art-bf2a620753274ea4a2392fce368c8a7f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bf2a620753274ea4a2392fce368c8a7f2025-08-20T04:03:03ZengNature PortfolioNature Communications2041-17232025-07-0116111910.1038/s41467-025-62046-9Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesisPatrick van Nierop y Sanchez0Pallavi Santhi Sekhar1Kerem Yildirim2Tim Lange3Laura Zoe Kreplin4Vigneshwarr Muruga Boopathy5Stephanie Rosswag de Souza6Kim Dammer7David Ibberson8Qian Wang9Katrin Domsch10Anniek Stokkermans11Shubhanshu Pandey12Petra Kaspar13Rafael Martinez-Gallegos14Xuefan Gao15Aakriti Singh16Natalja Engel17Fillip Port18Michael Boutros19Josephine Bageritz20Ingrid Lohmann21Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceDeep Sequencing Core Facility, BioQuant, Heidelberg UniversityHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHubrecht Institute-KNAWHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Stem Cell Niche HeterogeneityGerman Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and University of Heidelberg, Department of Cell and Molecular BiologyGerman Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and University of Heidelberg, Department of Cell and Molecular BiologyGerman Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and University of Heidelberg, Department of Cell and Molecular BiologyHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks—Cluster of ExcellenceAbstract Cellular decision-making and tissue homeostasis are governed by transcriptional networks shaped by chromatin accessibility. Using single-nucleus multi-omics, we jointly profile gene expression and chromatin accessibility in 10,335 cells from the Drosophila testis apical tip. This enables inference of 147 cell type-specific enhancer-gene regulons using SCENIC + . We functionally validate key transcription factors, including ovo and klumpfuss, known from other stem cell systems but not previously linked to spermatogenesis. CRISPR-mediated knockout reveals their essential roles in germline stem cell regulation, and we provide evidence that they co-regulate shared targets through overlapping enhancer elements. We further uncover a critical role for canonical Wnt signaling, with Pangolin/Tcf activating lineage-specific targets in the germline, soma, and niche. The Pan eRegulon links Wnt activity to cell adhesion, intercellular signaling and germline stem cell maintenance. Together, our study defines the enhancer-driven regulatory landscape of early spermatogenesis and reveals conserved, combinatorial mechanisms of niche-dependent stem cell control.https://doi.org/10.1038/s41467-025-62046-9 |
| spellingShingle | Patrick van Nierop y Sanchez Pallavi Santhi Sekhar Kerem Yildirim Tim Lange Laura Zoe Kreplin Vigneshwarr Muruga Boopathy Stephanie Rosswag de Souza Kim Dammer David Ibberson Qian Wang Katrin Domsch Anniek Stokkermans Shubhanshu Pandey Petra Kaspar Rafael Martinez-Gallegos Xuefan Gao Aakriti Singh Natalja Engel Fillip Port Michael Boutros Josephine Bageritz Ingrid Lohmann Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis Nature Communications |
| title | Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis |
| title_full | Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis |
| title_fullStr | Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis |
| title_full_unstemmed | Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis |
| title_short | Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis |
| title_sort | dissecting the enhancer gene regulatory network in early drosophila spermatogenesis |
| url | https://doi.org/10.1038/s41467-025-62046-9 |
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