A latent activated olfactory stem cell state revealed by single-cell transcriptomic and epigenomic profiling

Affiliations

¹ Department of Statistics, University of California, Berkeley, Berkeley, CA, USA; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
² Molecular Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
³ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
⁴ Department of Statistical Sciences, University of Padova, Padova, Italy.
⁵ Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.
⁷ Department of Statistics, University of California, Berkeley, Berkeley, CA, USA; Division of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
⁸ Molecular Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: john.ngai@nih.gov.
⁹ Molecular Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: whitney.heavner@nih.gov.

PMID: 41512864
DOI: 10.1016/j.stemcr.2025.102778

Free article

A latent activated olfactory stem cell state revealed by single-cell transcriptomic and epigenomic profiling

Koen Van den Berge et al. Stem Cell Reports. 2026.

Free article

. 2026 Jan 8:102778.

doi: 10.1016/j.stemcr.2025.102778. Online ahead of print.

Authors

Affiliations

¹ Department of Statistics, University of California, Berkeley, Berkeley, CA, USA; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
² Molecular Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
³ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
⁴ Department of Statistical Sciences, University of Padova, Padova, Italy.
⁵ Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.
⁷ Department of Statistics, University of California, Berkeley, Berkeley, CA, USA; Division of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
⁸ Molecular Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: john.ngai@nih.gov.
⁹ Molecular Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: whitney.heavner@nih.gov.

PMID: 41512864
DOI: 10.1016/j.stemcr.2025.102778

Abstract

The olfactory epithelium is one of the few regions of the nervous system that sustains neurogenesis throughout life. Its experimental accessibility makes it especially tractable for studying molecular mechanisms that drive neural regeneration in response to injury. In this study, we used single-cell sequencing to identify transcriptional and epigenetic processes involved in determining olfactory epithelial stem cell fate during injury-induced regeneration. By combining gene expression and accessible chromatin profiles of individual lineage-traced olfactory stem cells, we identified transcriptional heterogeneity among activated stem cells at a stage when cell fates are being specified. We further identified a subset of resting cells that appears poised for activation, characterized by accessible chromatin around silent genes prior to their expression in response to injury. These results provide evidence for a latent activated stem cell state in which a subset of quiescent olfactory epithelial stem cells are epigenetically primed to support injury-induced regeneration.

Keywords: adult tissue stem cell; epigenetic; epigenomics; horizontal basal cell; neural regeneration; neurogenesis; olfactory; olfactory epithelium; olfactory stem cell; regeneration; single-cell ATAC-seq; single-cell RNA-seq.

Published by Elsevier Inc.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

A Latent Activated Olfactory Stem Cell State Revealed by Single-Cell Transcriptomic and Epigenomic Profiling.
Van den Berge K, Bakalar D, Chou HJ, Kunda D, Risso D, Street K, Purdom E, Dudoit S, Ngai J, Heavner W. Van den Berge K, et al. bioRxiv [Preprint]. 2025 Mar 13:2023.10.26.564041. doi: 10.1101/2023.10.26.564041. bioRxiv. 2025. Update in: Stem Cell Reports. 2026 Jan 8:102778. doi: 10.1016/j.stemcr.2025.102778. PMID: 37961539 Free PMC article. Updated. Preprint.

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A latent activated olfactory stem cell state revealed by single-cell transcriptomic and epigenomic profiling

Affiliations

A latent activated olfactory stem cell state revealed by single-cell transcriptomic and epigenomic profiling

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

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Full Text Sources