TY  - JOUR
AU  - van Nierop Y Sanchez, Patrick
AU  - Sekhar, Pallavi Santhi
AU  - Yildirim, Kerem
AU  - Lange, Tim
AU  - Kreplin, Laura Zoe
AU  - Boopathy, Vigneshwarr Muruga
AU  - Rosswag de Souza, Stephanie
AU  - Dammer, Kim
AU  - Ibberson, David
AU  - Wang, Qian
AU  - Domsch, Katrin
AU  - Stokkermans, Anniek
AU  - Pandey, Shubhanshu
AU  - Kaspar, Petra
AU  - Martinez-Gallegos, Rafael
AU  - Gao, Xuefan
AU  - Singh, Aakriti
AU  - Engel, Natalja
AU  - Port, Fillip
AU  - Boutros, Michael
AU  - Bageritz, Josephine
AU  - Lohmann, Ingrid
TI  - Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01517
SP  - 6766
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Male
KW  - Spermatogenesis: genetics
KW  - Enhancer Elements, Genetic: genetics
KW  - Gene Regulatory Networks
KW  - Drosophila Proteins: genetics
KW  - Drosophila Proteins: metabolism
KW  - Testis: metabolism
KW  - Testis: cytology
KW  - Wnt Signaling Pathway: genetics
KW  - Gene Expression Regulation, Developmental
KW  - Transcription Factors: metabolism
KW  - Transcription Factors: genetics
KW  - Drosophila melanogaster: genetics
KW  - Stem Cells: metabolism
KW  - Stem Cells: cytology
KW  - Germ Cells: metabolism
KW  - Drosophila Proteins (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40695849
DO  - DOI:10.1038/s41467-025-62046-9
UR  - https://inrepo02.dkfz.de/record/303092
ER  -