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Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis

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 o...

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Main Authors: Nierop y Sanchez, Patrick van (Author) , Santhi Sekhar, Pallavi (Author) , Yildirim, Kerem (Author) , Lange, Tim (Author) , Kreplin, Laura Zoe (Author) , Muruga Boopathy, Vigneshwarr (Author) , Rosswag de Souza, Stephanie (Author) , Dammer, Kim (Author) , Ibberson, David (Author) , Wang, Qian (Author) , Domsch, Katrin (Author) , Stokkermans, Anniek (Author) , Pandey, Shubhanshu (Author) , Kaspar, Petra (Author) , Martinez-Gallegos, Rafael (Author) , Gao, Xuefan (Author) , Singh, Aakriti (Author) , Engel, Natalja (Author) , Port, Fillip (Author) , Boutros, Michael (Author) , Bageritz, Josephine (Author) , Lohmann, Ingrid (Author)
Format: Article (Journal)
Language:English
Published: 23 July 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-19
ISSN:2041-1723
DOI:10.1038/s41467-025-62046-9
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-62046-9
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-62046-9
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Author Notes: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
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Summary: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.
Item Description:Veröffentlicht: 23. Juli 2025
Gesehen am 19.11.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-62046-9

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