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A Single-Cell Transcriptomic Atlas of Human Neocortical Development during Mid-gestation.
Polioudakis, Damon; de la Torre-Ubieta, Luis; Langerman, Justin; Elkins, Andrew G; Shi, Xu; Stein, Jason L; Vuong, Celine K; Nichterwitz, Susanne; Gevorgian, Melinda; Opland, Carli K; Lu, Daning; Connell, William; Ruzzo, Elizabeth K; Lowe, Jennifer K; Hadzic, Tarik; Hinz, Flora I; Sabri, Shan; Lowry, William E; Gerstein, Mark B; Plath, Kathrin; Geschwind, Daniel H.
Affiliation
  • Polioudakis D; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • de la Torre-Ubieta L; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Langerman J; Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Elkins AG; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Shi X; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
  • Stein JL; Department of Genetics & UNC Neuroscience Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
  • Vuong CK; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA.
  • Nichterwitz S; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Gevorgian M; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Biology, CSUN, Northridge, CA, USA.
  • Opland CK; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Lu D; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Connell W; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Ruzzo EK; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Lowe JK; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Hadzic T; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Hinz FI; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Sabri S; Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Lowry WE; Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA.
  • Gerstein MB; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA; Department of Statistics and Data
  • Plath K; Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Geschwind DH; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. Ele
Neuron ; 103(5): 785-801.e8, 2019 09 04.
Article in En | MEDLINE | ID: mdl-31303374
ABSTRACT
We performed RNA sequencing on 40,000 cells to create a high-resolution single-cell gene expression atlas of developing human cortex, providing the first single-cell characterization of previously uncharacterized cell types, including human subplate neurons, comparisons with bulk tissue, and systematic analyses of technical factors. These data permit deconvolution of regulatory networks connecting regulatory elements and transcriptional drivers to single-cell gene expression programs, significantly extending our understanding of human neurogenesis, cortical evolution, and the cellular basis of neuropsychiatric disease. We tie cell-cycle progression with early cell fate decisions during neurogenesis, demonstrating that differentiation occurs on a transcriptomic continuum; rather than only expressing a few transcription factors that drive cell fates, differentiating cells express broad, mixed cell-type transcriptomes before telophase. By mapping neuropsychiatric disease genes to cell types, we implicate dysregulation of specific cell types in ASD, ID, and epilepsy. We developed CoDEx, an online portal to facilitate data access and browsing.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Developmental / Neocortex / Databases, Genetic / Gene Regulatory Networks / Neurogenesis / Neurons Type of study: Prognostic_studies Limits: Female / Humans / Pregnancy Language: En Journal: Neuron Journal subject: NEUROLOGIA Year: 2019 Type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Developmental / Neocortex / Databases, Genetic / Gene Regulatory Networks / Neurogenesis / Neurons Type of study: Prognostic_studies Limits: Female / Humans / Pregnancy Language: En Journal: Neuron Journal subject: NEUROLOGIA Year: 2019 Type: Article Affiliation country: United States