title: Integrative Single-Cell Transcriptomics Reveals Molecular Networks Defining Neuronal Maturation During Postnatal Neurogenesis.
abstract: In mammalian hippocampus, new neurons are continuously produced from neural stem cells throughout life. This postnatal neurogenesis may contribute to information processing critical for cognition, adaptation, learning, and memory, and is implicated in numerous neurological disorders. During neurogenesis, the immature neuron stage defined by doublecortin (DCX) expression is the most sensitive to regulation by extrinsic factors. However, little is known about the dynamic biology within this critical interval that drives maturation and confers susceptibility to regulatory signals. This study aims to test the hypothesis that DCX-expressing immature neurons progress through developmental stages via activity of specific transcriptional networks. Using single-cell RNA-seq combined with a novel integrative bioinformatics approach, we discovered that individual immature neurons can be classified into distinct developmental subgroups based on characteristic gene expression profiles and subgroup-specific markers. Comparisons between immature and more mature subgroups revealed novel pathways involved in neuronal maturation. Genes enriched in less mature cells shared significant overlap with genes implicated in neurodegenerative diseases, while genes positively associated with neuronal maturation were enriched for autism-related gene sets. Our study thus discovers molecular signatures of individual immature neurons and unveils potential novel targets for therapeutic approaches to treat neurodevelopmental and neurological diseases.
authors.affiliation: Waisman Center.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Waisman Center.|State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Waisman Center.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Eisinger
authors.affiliation: Waisman Center.
authors.forename: Laurel E
authors.initials: LE
authors.lastname: Kelnhofer
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.|Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Jobe
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.|Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.|Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D057205:Automation, Laboratory; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D020869:Gene Expression Profiling / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D025341:Principal Component Analysis; D059010:Single-Cell Analysis / Q000379:methods
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: doublecortin; neurogenesis; neuronal maturation; single-cell RNA-seq; transcriptome