Journal Article

DKFZ-2025-01517

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis.

van Nierop Y Sanchez, P. ; Sekhar, P. S. ; Yildirim, K. ; Lange, T. ; Kreplin, L. Z. ; Boopathy, V. M. ; Rosswag de Souza, S. ; Dammer, K. ; Ibberson, D. ; Wang, Q. ; Domsch, K. ; Stokkermans, A. ; Pandey, S. ; Kaspar, P. ; Martinez-Gallegos, R. ; Gao, X. ; Singh, A. ; Engel, N. ; Port, F.DKFZ* ; Boutros, M.DKFZ* ; Bageritz, J.DKFZ* ; Lohmann, I.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-62046-9

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.

Keyword(s): Animals (MeSH) ; Male (MeSH) ; Spermatogenesis: genetics (MeSH) ; Enhancer Elements, Genetic: genetics (MeSH) ; Gene Regulatory Networks (MeSH) ; Drosophila Proteins: genetics (MeSH) ; Drosophila Proteins: metabolism (MeSH) ; Testis: metabolism (MeSH) ; Testis: cytology (MeSH) ; Wnt Signaling Pathway: genetics (MeSH) ; Gene Expression Regulation, Developmental (MeSH) ; Transcription Factors: metabolism (MeSH) ; Transcription Factors: genetics (MeSH) ; Drosophila melanogaster: genetics (MeSH) ; Stem Cells: metabolism (MeSH) ; Stem Cells: cytology (MeSH) ; Germ Cells: metabolism (MeSH) ; Drosophila Proteins ; Transcription Factors

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Contributing Institute(s):

1. B110 Signalwege funktionelle Genomik (B110)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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