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Single cell enhancer activity distinguishes GABAergic and cholinergic lineages in embryonic mouse basal ganglia.
Su-Feher, Linda; Rubin, Anna N; Silberberg, Shanni N; Catta-Preta, Rinaldo; Lim, Kenneth J; Ypsilanti, Athena R; Zdilar, Iva; McGinnis, Christopher S; McKinsey, Gabriel L; Rubino, Thomas E; Hawrylycz, Michael J; Thompson, Carol; Gartner, Zev J; Puelles, Luis; Zeng, Hongkui; Rubenstein, John L R; Nord, Alex S.
Affiliation
  • Su-Feher L; Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95616.
  • Rubin AN; Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616.
  • Silberberg SN; Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, CA 94143.
  • Catta-Preta R; Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, CA 94143.
  • Lim KJ; Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95616.
  • Ypsilanti AR; Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616.
  • Zdilar I; Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95616.
  • McGinnis CS; Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616.
  • McKinsey GL; Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, CA 94143.
  • Rubino TE; Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, CA 94143.
  • Hawrylycz MJ; Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95616.
  • Thompson C; Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616.
  • Gartner ZJ; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143.
  • Puelles L; Department of Pediatrics, University of California, San Francisco, CA 94143.
  • Zeng H; Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95616.
  • Rubenstein JLR; Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616.
  • Nord AS; Allen Institute for Brain Science, Seattle, WA 98109.
Proc Natl Acad Sci U S A ; 119(15): e2108760119, 2022 04 12.
Article in En | MEDLINE | ID: mdl-35377797
Enhancers integrate transcription factor signaling pathways that drive cell fate specification in the developing brain. We paired enhancer labeling and single-cell RNA-sequencing (scRNA-seq) to delineate and distinguish specification of neuronal lineages in mouse medial, lateral, and caudal ganglionic eminences (MGE, LGE, and CGE) at embryonic day (E)11.5. We show that scRNA-seq clustering using transcription factors improves resolution of regional and developmental populations, and that enhancer activities identify specific and overlapping GE-derived neuronal populations. First, we mapped the activities of seven evolutionarily conserved brain enhancers at single-cell resolution in vivo, finding that the selected enhancers had diverse activities in specific progenitor and neuronal populations across the GEs. We then applied enhancer-based labeling, scRNA-seq, and analysis of in situ hybridization data to distinguish transcriptionally distinct and spatially defined subtypes of MGE-derived GABAergic and cholinergic projection neurons and interneurons. Our results map developmental origins and specification paths underlying neurogenesis in the embryonic basal ganglia and showcase the power of scRNA-seq combined with enhancer-based labeling to resolve the complex paths of neuronal specification underlying mouse brain development.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Basal Ganglia / Enhancer Elements, Genetic / Neurogenesis / Cholinergic Neurons / GABAergic Neurons Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Basal Ganglia / Enhancer Elements, Genetic / Neurogenesis / Cholinergic Neurons / GABAergic Neurons Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Type: Article