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| Status |
Public on May 05, 2020 |
| Title |
CRISPR-Mediated Multiplexed Epigenomic Perturbation of Putatively Functional ASoC Sites in Human Neural Progenitor Cell Model at Single-cell Resolution |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Functional interpretation of noncoding disease variants, which likely regulate gene expression, has been challenging. Chromatin accessibility (openness) strongly influences gene expression in neurodevelopment; however, to what extent genetic variants can alter chromatin openness in the context of brain disorders/traits is largely unknown. Using human induced pluripotent stem cell (iPSC)-derived neurons as a neurodevelopmental model, we identified abundant open-chromatin regions absent in brains and thousands of genetic variants exhibiting allele-specific open-chromatin (ASoC). ASoC variants are overrepresented in brain enhancers, transcription-factor-binding sites, and quantitative-trait-loci affecting histone modifications or DNA methylation. ASoC variants are also highly enriched for those associated with brain disorders/traits. Following-up schizophrenia-associated ASoC variants by multiplex epigenomic perturbation, computational fine-mapping, and CRISPR-editing further confirmed their regulatory activities and cis-targeted genes. Our study provides the first snapshot of neuronal ASoC landscape and a framework for prioritizing functional disease variants.
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| Overall design |
NPC samples were derived from individual cell line #05, #07, and #08. Collected NPC samples were processed with 10x Genomics Chromium Single Cell 3’ Reagent Kits v2 according to the manufacturer’s instructions. Sequencing of the prepared library was performed on an Illumina sequencer generating approximately 450M reads in total.
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| Contributor(s) |
Duan J, Zhang S |
| Citation(s) |
32732423, 34308291 |
| |
| Submission date |
Jun 14, 2019 |
| Last update date |
Jul 28, 2021 |
| Contact name |
Jubao Duan |
| E-mail(s) |
[email protected]
|
| Phone |
(224) 364-7564
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| Organization name |
NorthShore University HealthSystem
|
| Department |
Center for Psychiatric Genetics
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| Lab |
Unit of Functional Genomics in Psychiatry
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| Street address |
1001 University Place
|
| City |
Evanston |
| State/province |
IL |
| ZIP/Postal code |
60201 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA548928 |
| SRA |
SRP201467 |
