NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE232948 Query DataSets for GSE232948
Status Public on May 23, 2023
Title Cell type-specific cis-regulatory divergence in gene expression and chromatin accessibility revealed by human-chimpanzee hybrid cells [RNA-seq]
Organisms Pan troglodytes; Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell type-specific cis-regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell type, avoiding the potentially deleterious consequences of trans-acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively. It has recently become possible to quantify human-specific cis-acting regulatory divergence by measuring allele-specific expression in human-chimpanzee hybrid cells—the product of fusing induced pluripotent stem (iPS) cells of each species in vitro. However, these cis-regulatory changes have only been explored in a limited number of tissues and cell types. Here, we quantify human-chimpanzee cis-regulatory divergence in gene expression and chromatin accessibility across six cell types, enabling the identification of highly cell type-specific cis-regulatory changes. We find that cell type-specific genes and regulatory elements evolve faster than those shared across cell types. Furthermore, we identify several instances of lineage-specific natural selection that may have played key roles in specific cell types, such as coordinated changes in the cis-regulation of dozens of genes involved in neuronal firing in motor neurons. Finally, using novel metrics and a machine learning model, we identify genetic variants that likely alter chromatin accessibility and transcription factor binding, leading to neuron-specific changes in the expression of the neurodevelopmentally important genes FABP7 and GAD1. Overall, our results demonstrate that integrative analysis of cis-regulatory divergence in chromatin accessibility and gene expression across cell types is a promising approach to identify the specific genes and genetic variants that make us human.
 
Overall design RNA sequencing of human-chimpanzee hybrid iPS cells derived six cell types
 
Contributor(s) Wang B, Starr AL, Fraser HB
Citation(s) 37292820, 38358392
Submission date May 19, 2023
Last update date Mar 20, 2024
Contact name Hunter Fraser
Organization name Stanford University
Street address 327 Campus Drive
City Stanford
ZIP/Postal code 94305
Country USA
 
Platforms (1)
GPL27803 Illumina HiSeq 4000 (Homo sapiens; Pan troglodytes)
Samples (25)
GSM7398430 Hybrid Cardiomyocte, Hybrid1, rep1
GSM7398431 Hybrid Cardiomyocte, Hybrid2, rep1
GSM7398432 Hybrid Skeletal myocyte, Hybrid1, rep1
This SubSeries is part of SuperSeries:
GSE232949 Cell type-specific cis-regulatory divergence in gene expression and chromatin accessibility revealed by human-chimpanzee hybrid cells
Relations
BioProject PRJNA974466

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE232948_RNAseq_ASE_CM_HP_MN_PP_SKM_RPE_GRCh38.txt.gz 3.5 Mb (ftp)(http) TXT
GSE232948_RNAseq_ASE_CM_HP_MN_PP_SKM_RPE_PanTro6.txt.gz 3.5 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap