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Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus.
Herb, Brian R; Glover, Hannah J; Bhaduri, Aparna; Colantuoni, Carlo; Bale, Tracy L; Siletti, Kimberly; Hodge, Rebecca; Lein, Ed; Kriegstein, Arnold R; Doege, Claudia A; Ament, Seth A.
  • Herb BR; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Glover HJ; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Bhaduri A; UM-MIND, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Colantuoni C; Kahlert Institute for Addiction Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Bale TL; Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
  • Siletti K; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hodge R; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Lein E; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kriegstein AR; Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA.
  • Doege CA; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Ament SA; Allen Institute for Brain Science, Seattle, WA 98109.
Sci Adv ; 9(45): eadf6251, 2023 11 10.
Article en En | MEDLINE | ID: mdl-37939194
ABSTRACT
The development and diversity of neuronal subtypes in the human hypothalamus has been insufficiently characterized. To address this, we integrated transcriptomic data from 241,096 cells (126,840 newly generated) in the prenatal and adult human hypothalamus to reveal a temporal trajectory from proliferative stem cell populations to mature hypothalamic cell types. Iterative clustering of the adult neurons identified 108 robust transcriptionally distinct neuronal subtypes representing 10 hypothalamic nuclei. Pseudotime trajectories provided insights into the genes driving formation of these nuclei. Comparisons to single-cell transcriptomic data from the mouse hypothalamus suggested extensive conservation of neuronal subtypes despite certain differences in species-enriched gene expression. The uniqueness of hypothalamic neuronal lineages was examined developmentally by comparing excitatory lineages present in cortex and inhibitory lineages in ganglionic eminence, revealing both distinct and shared drivers of neuronal maturation across the human forebrain. These results provide a comprehensive transcriptomic view of human hypothalamus development through gestation and adulthood at cellular resolution.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Hipotálamo / Neuronas Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Hipotálamo / Neuronas Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article