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Series GSE146481 Query DataSets for GSE146481
Status Public on Oct 09, 2020
Title Human-chimpanzee hybrid cells reveal gene regulatory evolution underlying skeletal divergence
Organisms Pan troglodytes; Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Gene regulatory divergence is thought to play a central role in determining human-specific traits. However, our ability to link divergent regulation to divergent phenotypes is limited. Here, we utilized human-chimpanzee hybrid induced pluripotent stem cells to study divergent gene expression separating these species. The hybrid cells allowed us to separate cis- from trans-regulatory effects, and to control for non-genetic factors that often confound comparative studies. We differentiated these cells into cranial neural crest cells (CNCCs), the primary cell type giving rise to the face, and used the hybrid cells to generate a catalogue of divergent cis-regulatory gene expression between humans and chimpanzees. We found that cis-regulatory divergence is tightly linked to phenotypic divergence, enabling the identification of candidate genes associated with several divergent traits. Specifically, we find support for lineage-specific selection acting on the cis-regulation of the hedgehog signaling pathway. This pathway includes EVC2 (LIMBIN), whose cis-regulation is among the most divergent in the genome, resulting in 6-fold down-regulation along the human lineage. We found that inducing a similar reduction in EVC2 levels substantially reduces Hh signaling output. Mice and humans lacking functional EVC2 show striking parallels to many human-chimpanzee phenotypic differences, particularly in the skull and face, suggesting that the regulatory divergence of Hh signaling may have contributed to the unique craniofacial morphology of humans. In sum, our results suggest that human-chimpanzee hybrid cells can serve as a valuable resource to study the evolution of gene regulation and its impact on phenotypic divergence. SRA/fastq files include Illumina adapters (GATCGGAAGAGCACACGTCT and GATCGGAAGAGCGTCGTGTA).
 
Overall design RNA sequencing of iPSC-derived cranial neural crest cells (CNCCs) from three triplicates of human, chimpanzee and human-chimpanzee hybrid
 
Contributor(s) Gokhman D, Fraser H
Citation(s) 33731941
Submission date Mar 05, 2020
Last update date Dec 20, 2021
Contact name David Gokhman
E-mail(s) david.gokhman@mail.huji.ac.il
Organization name The Hebrew University of Jerusalem
Street address Givat Ram, Safra Campus
City Jerusalem
ZIP/Postal code 91904
Country Israel
 
Platforms (3)
GPL20795 HiSeq X Ten (Homo sapiens)
GPL28127 HiSeq X Ten (Pan troglodytes)
GPL28128 HiSeq X Ten (Homo sapiens; Pan troglodytes)
Samples (9)
GSM4386931 Human1_1_CNCCs
GSM4386932 Human1_2_CNCCs
GSM4386933 Human1_3_CNCCs
Relations
BioProject PRJNA610639
SRA SRP251762

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
GSE146481_ProcessedData_GEO.xlsx 85.6 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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