Single-cell multiomic approaches define a gradual, spatially regulated epigenetic and transcriptional transition from embryonic to adult neural stem cells.

Beatrix S Wang, Konstantina Karamboulas, Nareh Tahmasian, Daniel J Dennis, David R Kaplan, Freda D Miller

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Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Beatrix S WangMichael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.

Konstantina KaramboulasProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Nareh TahmasianProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.

Daniel J DennisProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

David R KaplanProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Freda D MillerMichael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: freda.miller@msl.ubc.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Here, we ask how adult neural stem cells (NSCs) arise developmentally, focusing on murine cortical precursors that generate excitatory neurons embryonically and interneurons and glial cells postnatally. Using complementary single-cell spatial, transcriptomic, and epigenomic approaches, we show that postnatal NSC state acquisition involves a gradual transcriptional and epigenetic shift in the entire embryonic cortical precursor cell population and identify a distinct transition precursor state at E17/18 when both embryonic and the first postnatal progeny are being generated. Non-proliferative adult NSCs are also first seen at this transition timepoint, but they arise in a spatial domain distinct from that of the first postnatal progeny, indicating that NSC state acquisition is not a necessary prelude to the switch in cell genesis. These findings support a gradual epigenetically continuous model for the transition from developing cortical precursors to NSCs and show that this is spatially separable from the transition to generating postnatal cell types.

Indexed as

Adult Stem CellsEmbryonic Stem CellsEpigenesis, GeneticNeural Stem CellsSingle-Cell AnalysisTranscription, GeneticAnimalsCell DifferentiationGene Expression Regulation, DevelopmentalMiceMultiomicsNeurodevelopmentNeurogenesisSingle-Cell Gene Expression AnalysisTranscriptomecortical developmentneural stem cellsolfactory neurogenesisradial gliasingle-cell epigeneticssingle-cell spatial transcriptomicssingle-cell transcriptomicsstem cell developmentstem cell epigenetics

Identifiers

PMID42314674

DOI10.1016/j.stemcr.2026.102967

PMCPMC13385433

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LicenceCC BY-NC-ND

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.