%0 Journal Article
%A van Nierop Y Sanchez, Patrick
%A Sekhar, Pallavi Santhi
%A Yildirim, Kerem
%A Lange, Tim
%A Kreplin, Laura Zoe
%A Boopathy, Vigneshwarr Muruga
%A Rosswag de Souza, Stephanie
%A Dammer, Kim
%A Ibberson, David
%A Wang, Qian
%A Domsch, Katrin
%A Stokkermans, Anniek
%A Pandey, Shubhanshu
%A Kaspar, Petra
%A Martinez-Gallegos, Rafael
%A Gao, Xuefan
%A Singh, Aakriti
%A Engel, Natalja
%A Port, Fillip
%A Boutros, Michael
%A Bageritz, Josephine
%A Lohmann, Ingrid
%T Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DKFZ-2025-01517
%P 6766
%D 2025
%X 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.
%K Animals
%K Male
%K Spermatogenesis: genetics
%K Enhancer Elements, Genetic: genetics
%K Gene Regulatory Networks
%K Drosophila Proteins: genetics
%K Drosophila Proteins: metabolism
%K Testis: metabolism
%K Testis: cytology
%K Wnt Signaling Pathway: genetics
%K Gene Expression Regulation, Developmental
%K Transcription Factors: metabolism
%K Transcription Factors: genetics
%K Drosophila melanogaster: genetics
%K Stem Cells: metabolism
%K Stem Cells: cytology
%K Germ Cells: metabolism
%K Drosophila Proteins (NLM Chemicals)
%K Transcription Factors (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40695849
%R 10.1038/s41467-025-62046-9
%U https://inrepo02.dkfz.de/record/303092