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@ARTICLE{vanNieropYSanchez:303092,
author = {P. van Nierop Y Sanchez and P. S. Sekhar and K. Yildirim
and T. Lange and L. Z. Kreplin and V. M. Boopathy and S.
Rosswag de Souza and K. Dammer and D. Ibberson and Q. Wang
and K. Domsch and A. Stokkermans and S. Pandey and P. Kaspar
and R. Martinez-Gallegos and X. Gao and A. Singh and N.
Engel and F. Port$^*$ and M. Boutros$^*$ and J. Bageritz$^*$
and I. Lohmann},
title = {{D}issecting the enhancer gene regulatory network in early
{D}rosophila spermatogenesis.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01517},
pages = {6766},
year = {2025},
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.},
keywords = {Animals / Male / Spermatogenesis: genetics / Enhancer
Elements, Genetic: genetics / Gene Regulatory Networks /
Drosophila Proteins: genetics / Drosophila Proteins:
metabolism / Testis: metabolism / Testis: cytology / Wnt
Signaling Pathway: genetics / Gene Expression Regulation,
Developmental / Transcription Factors: metabolism /
Transcription Factors: genetics / Drosophila melanogaster:
genetics / Stem Cells: metabolism / Stem Cells: cytology /
Germ Cells: metabolism / Drosophila Proteins (NLM Chemicals)
/ Transcription Factors (NLM Chemicals)},
cin = {B110},
ddc = {500},
cid = {I:(DE-He78)B110-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40695849},
doi = {10.1038/s41467-025-62046-9},
url = {https://inrepo02.dkfz.de/record/303092},
}