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- Study Description
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Important Links and Information
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- Instructions for requestors
- Data Use Certification (DUC) Agreement
- Talking Glossary of Genetic Terms
Defining the number, proportion, or lineage of distinct cell types in the developing human brain is an important goal of modern brain research. We produced single cell transcriptomic profiles for 40,000 cells at mid-gestation to define deep expression profiles corresponding to all known major cell types at this developmental period and compare this with bulk tissue profiles. We identified multiple transcription factors (TFs) and co-factors expressed in specific cell types, including multiple new cell-type-specific relationships, providing an unprecedented resource for understanding human neocortical development and evolution. This includes the first single-cell characterization of human subplate neurons and subtypes of developing glutamatergic and GABAergic neurons. We also used these data to deconvolute single cell regulatory networks that connect regulatory elements and transcriptional drivers to single cell gene expression programs in the developing CNS. We characterized major developmental trajectories that tie cell cycle progression with early cell fate decisions during early neurogenesis. Remarkably, we found that differentiation occurs on a transcriptomic continuum, so that differentiating cells not only express the few key TFs that drive cell fates, but express broad, mixed cell-type transcriptomes prior to telophase. Finally, we mapped neuropsychiatric disease genes to specific cell types, implicating dysregulation of specific cell types in ASD, ID, and epilepsy, as the mechanistic underpinnings of several neurodevelopmental disorders. Together these results provide an extensive catalog of cell types in human neocortex and extend our understanding of early cortical development, human brain evolution and the cellular basis of neuropsychiatric disease.
- Study Design:
- Prospective Longitudinal Cohort
- Study Type:
- Cohort
- Total number of consented subjects: 4
- Subject Sample Telemetry Report (SSTR)
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- Authorized Access
- Publicly Available Data
- Link to other NCBI resources related to this study
- Study Inclusion/Exclusion Criteria
De-identified fetal tissue samples were obtained from the UCLA Gene and Cell Therapy Core according to IRB guidelines. No known major pathogenic CNVs implicated in neuropsychiatric disorders were found in these donors.
- Molecular Data
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Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment RNA Sequencing Illumina HiSeq 2500 N/A N/A Drop-seq was run on single cells according to the online Drop-seq protocol v.3.1. Libraries were prepared with the Nextera XT DNA Library Preparation Kit (Illumina). - Study History
This is the first and only data release for this study.
- Selected Publications
- Diseases/Traits Related to Study (MeSH terms)
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- Primary Phenotype: Autism Spectrum Disorder
- Schizophrenia
- Intellectual disability
- Epilepsy
- Links to Related Genes
- Authorized Data Access Requests
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See articles in PMC citing this study accession
- Study Attribution
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Principal Investigator
- Daniel H. Geschwind, MD, PhD. University of California, Los Angeles, Los Angeles, CA, USA.
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Funding Sources
- 1U01 MH105991. National Institutes of Health, Bethesda, MD, USA.
- 5R01 MH081754. National Institutes of Health, Bethesda, MD, USA.
- 5R01 MH100027. National Institutes of Health, Bethesda, MD, USA.
- 1R01MH110927. National Institutes of Health, Bethesda, MD, USA.
- 1U01MH116489. National Institutes of Health, Bethesda, MD, USA.
- Allen Distinguished Investigator Program. The Allen Institute, Seattle, WA, USA.
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Principal Investigator