A single-nucleus multiomic and spatial atlas of gene regulation in human spermatogenesis
- 1MRC Laboratory of Medical Sciences, London, UK
Abstract
Gametogenesis, the production of oocytes and sperm, ensures the faithful transmission of genetic material to the next generation. In males, spermatogenesis occurs within the testis, where germ cells progress through a highly ordered developmental programme in close association with supporting somatic cells. Defects in this process cause infertility, yet the gene regulatory mechanisms coordinating normal and dysfunctional human spermatogenesis remain incompletely defined. Here we generate a single-nucleus multiomic and spatial atlas of human spermatogenesis by profiling chromatin accessibility and gene expression in the same nuclei and integrating these data with spatial transcriptomics of intact testicular tissue. We infer high-confidence gene regulatory networks that resolve stage-specific activity of known and novel candidate regulators across germline and somatic compartments, and map spatially restricted signalling interactions within the seminiferous tubule niche. Integration with infertility-associated genetic variation links non-coding risk loci to candidate enhancers and target genes in cell-type-specific regulatory contexts. Finally, profiling clinical cryptozoospermia samples as in vivo perturbations supports the ability of this network to capture downstream transcriptional consequences of disease-associated regulatory disruption. Together, these data provide a spatially resolved regulatory framework for human spermatogenesis and a foundation for interpreting the molecular basis of male infertility.
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BibTeX
@misc{bhaskaran2026singlenucleus,
title = {{A single-nucleus multiomic and spatial atlas of gene regulation in human spermatogenesis}},
author = {J. Bhaskaran and E. Ing-Simmons and I. Balaguer Balsells and S. Di Persio and M. M. Chan and M. Politz and J.-F. Cremers and N. Rotte and S. Kliesch and C. Friedrich and F. Tuettelmann and C. Ernst and S. Laurentino and N. Neuhaus and J. M. Vaquerizas},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749409},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749409v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A single-nucleus multiomic and spatial atlas of gene regulation in human spermatogenesis
AU - J. Bhaskaran
AU - E. Ing-Simmons
AU - I. Balaguer Balsells
AU - S. Di Persio
AU - M. M. Chan
AU - M. Politz
AU - J.-F. Cremers
AU - N. Rotte
AU - S. Kliesch
AU - C. Friedrich
AU - F. Tuettelmann
AU - C. Ernst
AU - S. Laurentino
AU - N. Neuhaus
AU - J. M. Vaquerizas
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749409
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749409v1
AB - Gametogenesis, the production of oocytes and sperm, ensures the faithful transmission of genetic material to the next generation. In males, spermatogenesis occurs within the testis, where germ cells progress through a highly ordered developmental programme in close association with supporting somatic cells. Defects in this process cause infertility, yet the gene regulatory mechanisms coordinating normal and dysfunctional human spermatogenesis remain incompletely defined. Here we generate a single-nucleus multiomic and spatial atlas of human spermatogenesis by profiling chromatin accessibility and gene expression in the same nuclei and integrating these data with spatial transcriptomics of intact testicular tissue. We infer high-confidence gene regulatory networks that resolve stage-specific activity of known and novel candidate regulators across germline and somatic compartments, and map spatially restricted signalling interactions within the seminiferous tubule niche. Integration with infertility-associated genetic variation links non-coding risk loci to candidate enhancers and target genes in cell-type-specific regulatory contexts. Finally, profiling clinical cryptozoospermia samples as in vivo perturbations supports the ability of this network to capture downstream transcriptional consequences of disease-associated regulatory disruption. Together, these data provide a spatially resolved regulatory framework for human spermatogenesis and a foundation for interpreting the molecular basis of male infertility.
ER -