A single-nucleus regulatory atlas links transposable elements to adult hippocampal neurogenesis
- 1Institut Necker Enfants Malades (INEM), INSERM UMR 1151, Paris 75015, France; Central Institute of Mental Health, Heidelberg University, J 5, Mannheim, Germany;
Abstract
Adult hippocampal neurogenesis can be enhanced or even triggered by extrinsic stimuli, but the lineage-specific regulatory changes that accompany a stimulated neurogenic response remain undefined. We used recombinant human erythropoietin (rhEPO), a defined influencing factor that enriches newly formed pyramidal neurons by ~2 fold in this paradigm, to profile ~35,000 nuclei by single-nucleus ATAC sequencing (snATAC-seq) from rhEPO- and placebo-treated adult mouse hippocampi and to integrate them with matched single-nucleus RNA sequencing (snRNA-seq) of ~120,000 nuclei. Thirty-five accessibility-defined clusters resolved 11 major lineages. Of 39,404 differentially accessible regions (DARs), more than half arose in pyramidal neurons, whereas dentate gyrus granule neurons and interneurons showed predominantly reduced accessibility; within the pyramidal lineage, remodelling was predominant in newly-formed rather than mature neurons. About 20% of hippocampal candidate cis-regulatory elements (cCREs) overlapped transposable elements (TEs) at baseline, rising to about 50% among regions that gained accessibility upon stimulation, and multiple families were significantly bound above the expected threshold by neurogenic transcription factors, whereby the many neighbouring genes have established roles for neuronal differentiation and synapse formation. These data define TE-derived sequences as candidate components of stimulus-responsive neurogenic regulatory networks and provide a cell-type-specific chromatin resource for the adult hippocampus at single-nucleus resolution.
Related
- Pangenome-resolved polymorphic transposable elements reveal human regulatory evolution in action
- Transposable elements impact the human regulatory landscape through cell type specific epigenomic associations
- Transposable Elements Profiling Reveals DUXA-associated MLT1D Endogenous Retroviral Elements Activation During Bovine Maternal to Zygotic Transition
- Juvenile behavioral alterations and sex-dependent deficits in hippocampal neurogenesis following early-life stress in rats
- Prepubertal NMN Administration is associated with changes in hippocampal neurogenesis-related markers and amelioration of cognitive deficits
BibTeX
@misc{cakir2026singlenucleus,
title = {{A single-nucleus regulatory atlas links transposable elements to adult hippocampal neurogenesis}},
author = {U. Cakir and F. Mantovani and S. Y. Abadi and U. J. Butt and V. Bansal and R. Kawaguchi and D. Geschwind and K.-A. Nave and H. Ehrenreich and M. Singh},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748376},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748376v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A single-nucleus regulatory atlas links transposable elements to adult hippocampal neurogenesis
AU - U. Cakir
AU - F. Mantovani
AU - S. Y. Abadi
AU - U. J. Butt
AU - V. Bansal
AU - R. Kawaguchi
AU - D. Geschwind
AU - K.-A. Nave
AU - H. Ehrenreich
AU - M. Singh
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748376
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748376v1
AB - Adult hippocampal neurogenesis can be enhanced or even triggered by extrinsic stimuli, but the lineage-specific regulatory changes that accompany a stimulated neurogenic response remain undefined. We used recombinant human erythropoietin (rhEPO), a defined influencing factor that enriches newly formed pyramidal neurons by ~2 fold in this paradigm, to profile ~35,000 nuclei by single-nucleus ATAC sequencing (snATAC-seq) from rhEPO- and placebo-treated adult mouse hippocampi and to integrate them with matched single-nucleus RNA sequencing (snRNA-seq) of ~120,000 nuclei. Thirty-five accessibility-defined clusters resolved 11 major lineages. Of 39,404 differentially accessible regions (DARs), more than half arose in pyramidal neurons, whereas dentate gyrus granule neurons and interneurons showed predominantly reduced accessibility; within the pyramidal lineage, remodelling was predominant in newly-formed rather than mature neurons. About 20% of hippocampal candidate cis-regulatory elements (cCREs) overlapped transposable elements (TEs) at baseline, rising to about 50% among regions that gained accessibility upon stimulation, and multiple families were significantly bound above the expected threshold by neurogenic transcription factors, whereby the many neighbouring genes have established roles for neuronal differentiation and synapse formation. These data define TE-derived sequences as candidate components of stimulus-responsive neurogenic regulatory networks and provide a cell-type-specific chromatin resource for the adult hippocampus at single-nucleus resolution.
ER -