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Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms.
Patowary, Ashok; Zhang, Pan; Jops, Connor; Vuong, Celine K; Ge, Xinzhou; Hou, Kangcheng; Kim, Minsoo; Gong, Naihua; Margolis, Michael; Vo, Daniel; Wang, Xusheng; Liu, Chunyu; Pasaniuc, Bogdan; Li, Jingyi Jessica; Gandal, Michael J; de la Torre-Ubieta, Luis.
Afiliación
  • Patowary A; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Zhang P; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Jops C; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Vuong CK; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Ge X; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Hou K; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Kim M; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Gong N; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Margolis M; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Vo D; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Wang X; Lifespan Brain Institute at Penn Med and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Liu C; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Pasaniuc B; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Li JJ; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Gandal MJ; Department of Statistics, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • de la Torre-Ubieta L; Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA 90095, USA.
Science ; 384(6698): eadh7688, 2024 May 24.
Article en En | MEDLINE | ID: mdl-38781356
ABSTRACT
RNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders; yet, the role of cell type-specific splicing and transcript-isoform diversity during human brain development has not been systematically investigated. In this work, we leveraged single-molecule long-read sequencing to deeply profile the full-length transcriptome of the germinal zone and cortical plate regions of the developing human neocortex at tissue and single-cell resolution. We identified 214,516 distinct isoforms, of which 72.6% were novel (not previously annotated in Gencode version 33), and uncovered a substantial contribution of transcript-isoform diversity-regulated by RNA binding proteins-in defining cellular identity in the developing neocortex. We leveraged this comprehensive isoform-centric gene annotation to reprioritize thousands of rare de novo risk variants and elucidate genetic risk mechanisms for neuropsychiatric disorders.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Empalme del ARN / Neocórtex / Isoformas de Proteínas / Neurogénesis / Análisis de la Célula Individual / Transcriptoma / Trastornos Mentales Límite: Humans Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Empalme del ARN / Neocórtex / Isoformas de Proteínas / Neurogénesis / Análisis de la Célula Individual / Transcriptoma / Trastornos Mentales Límite: Humans Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos