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Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution.
Trevino, Alexandro E; Müller, Fabian; Andersen, Jimena; Sundaram, Laksshman; Kathiria, Arwa; Shcherbina, Anna; Farh, Kyle; Chang, Howard Y; Pașca, Anca M; Kundaje, Anshul; Pașca, Sergiu P; Greenleaf, William J.
Afiliación
  • Trevino AE; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Müller F; Department of Genetics, Stanford University, Stanford, CA, USA; Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
  • Andersen J; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Stanford Brain Organogenesis Program, Wu Tsai Neuroscience Institute Stanford University, Stanford, CA, USA.
  • Sundaram L; Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Kathiria A; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Shcherbina A; Biomedical Data Science Program, Stanford University, Stanford CA, USA.
  • Farh K; Illumina Artificial Intelligence Laboratory, Illumina Inc, San Diego, CA, USA.
  • Chang HY; Department of Genetics, Stanford University, Stanford, CA, USA; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
  • Pașca AM; Department of Pediatrics, Division of Neonatology, Stanford University, Stanford, CA, USA.
  • Kundaje A; Department of Genetics, Stanford University, Stanford, CA, USA; Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Pașca SP; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Stanford Brain Organogenesis Program, Wu Tsai Neuroscience Institute Stanford University, Stanford, CA, USA. Electronic address: spasca@stanford.edu.
  • Greenleaf WJ; Department of Genetics, Stanford University, Stanford, CA, USA; Department of Applied Physics, Stanford University, Stanford, CA, USA; Chan-Zuckerberg Biohub, San Francisco, CA, USA. Electronic address: wjg@stanford.edu.
Cell ; 184(19): 5053-5069.e23, 2021 09 16.
Article en En | MEDLINE | ID: mdl-34390642
ABSTRACT
Genetic perturbations of cortical development can lead to neurodevelopmental disease, including autism spectrum disorder (ASD). To identify genomic regions crucial to corticogenesis, we mapped the activity of gene-regulatory elements generating a single-cell atlas of gene expression and chromatin accessibility both independently and jointly. This revealed waves of gene regulation by key transcription factors (TFs) across a nearly continuous differentiation trajectory, distinguished the expression programs of glial lineages, and identified lineage-determining TFs that exhibited strong correlation between linked gene-regulatory elements and expression levels. These highly connected genes adopted an active chromatin state in early differentiating cells, consistent with lineage commitment. Base-pair-resolution neural network models identified strong cell-type-specific enrichment of noncoding mutations predicted to be disruptive in a cohort of ASD individuals and identified frequently disrupted TF binding sites. This approach illustrates how cell-type-specific mapping can provide insights into the programs governing human development and disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cromatina / Corteza Cerebral / Regulación del Desarrollo de la Expresión Génica / Análisis de la Célula Individual Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cromatina / Corteza Cerebral / Regulación del Desarrollo de la Expresión Génica / Análisis de la Célula Individual Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos