Duncan NRI Faculty and Staff Publications

Language

English

Publication Date

9-9-2025

Journal

Stem Cell Reports

DOI

10.1016/j.stemcr.2025.102606

PMID

40845852

PMCID

PMC12447325

PubMedCentral® Posted Date

8-21-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause Mendelian neurological conditions. In addition, leveraging a variety of computational tools and clinical and population databases, we identified 15 genes bearing novel damaging variants linked to neurological phenotypes, suggesting their potential role in contributing to human phenotypes. These discoveries illuminate NPC molecular underpinnings and underscore their relevance to both brain development and disease.

Keywords

Humans, Animals, Neural Stem Cells, Biomarkers, Mice, Computational Biology, Single-Cell Analysis, Neurogenesis, Hippocampus, dentate gyrus, neural stem cell, neuroprogenitors, neurogenesis, digital sorting, gene discovery, Mendelian diseases, undiagnosed diseases

Published Open-Access

yes

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