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Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis

Author

Listed:
  • Patrick Nierop y Sanchez

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Pallavi Santhi Sekhar

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Kerem Yildirim

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Tim Lange

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Laura Zoe Kreplin

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Vigneshwarr Muruga Boopathy

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Stephanie Rosswag de Souza

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Kim Dammer

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • David Ibberson

    (Heidelberg University)

  • Qian Wang

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Katrin Domsch

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Anniek Stokkermans

    (Hubrecht Institute-KNAW)

  • Shubhanshu Pandey

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Petra Kaspar

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Rafael Martinez-Gallegos

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Xuefan Gao

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Aakriti Singh

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

  • Natalja Engel

    (Department of Stem Cell Niche Heterogeneity)

  • Fillip Port

    (Department of Cell and Molecular Biology)

  • Michael Boutros

    (Department of Cell and Molecular Biology)

  • Josephine Bageritz

    (Department of Stem Cell Niche Heterogeneity)

  • Ingrid Lohmann

    (Department of Developmental Biology and Cell Networks—Cluster of Excellence)

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.

Suggested Citation

  • Patrick 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 &, 2025. "Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62046-9
    DOI: 10.1038/s41467-025-62046-9
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    References listed on IDEAS

    as
    1. Sarah Kimmins & Paolo Sassone-Corsi, 2005. "Chromatin remodelling and epigenetic features of germ cells," Nature, Nature, vol. 434(7033), pages 583-589, March.
    2. Jerome Korzelius & Sina Azami & Tal Ronnen-Oron & Philipp Koch & Maik Baldauf & Elke Meier & Imilce A. Rodriguez-Fernandez & Marco Groth & Pedro Sousa-Victor & Heinrich Jasper, 2019. "The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Florent Murat & Noe Mbengue & Sofia Boeg Winge & Timo Trefzer & Evgeny Leushkin & Mari Sepp & Margarida Cardoso-Moreira & Julia Schmidt & Celine Schneider & Katharina Mößinger & Thoomke Brüning & Fran, 2023. "The molecular evolution of spermatogenesis across mammals," Nature, Nature, vol. 613(7943), pages 308-316, January.
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