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| Status |
Public on Nov 29, 2021 |
| Title |
Genetic studies of human-chimpanzee divergence using stem cell fusions |
| Organisms |
Pan troglodytes; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Complete genome sequencing has identified millions of DNA changes that differ between humans and chimpanzees. Although a subset of these changes likely underlies important phenotypic differences between humans and chimpanzees, it is currently difficult to distinguish causal from incidental changes and to map specific phenotypes to particular genome locations. To facilitate further genetic study of human-chimpanzee divergence, we have generated human and chimpanzee auto-tetraploids and allo-tetraploids by fusing induced pluripotent stem cells (iPSCs) of each species. The resulting tetraploid iPSCs can be stably maintained and retain the ability to differentiate along ectoderm, mesoderm, and endoderm lineages. RNA sequencing identifies thousands of genes whose expression differs between humans and chimpanzees when assessed in single-species diploid or auto-tetraploid iPSCs. Analysis of gene expression patterns in inter-specific allo-tetraploid iPSCs shows that human-chimpanzee expression differences arise from substantial contributions of both cis-acting changes linked to the genes themselves, and trans-acting changes elsewhere in the genome. To enable further genetic mapping of species differences, we tested chemical treatments for stimulating genome-wide mitotic recombination between human and chimpanzee chromosomes, and CRISPR methods for inducing species-specific changes on particular chromosomes in allo-tetraploid cells. We successfully generated derivative cells with nested deletions or inter-specific recombination on the X chromosome. These studies identify a long distance cis-regulatory domain of the Fragile X-associated gene (FMR1), confirm an important role for the X chromosome in trans-regulation of other expression differences, and illustrate the potential of this system for more detailed mapping of the molecular basis of human and chimpanzee evolution.
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| Overall design |
Bulk RNA sequencing of human and chimpanzee diploid, auto-tetraploid, and allo-tetraploid iPSC lines
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| Contributor(s) |
Song JH, Grant RL, Behrens VC, Kucka M, Roberts Kingman GA, Soltys V, Chan YF, Kingsley DM |
| Citation(s) |
34921118 |
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| Submission date |
Sep 24, 2021 |
| Last update date |
Feb 28, 2022 |
| Contact name |
Janet Song |
| Organization name |
Boston Children's Hospital
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| Lab |
Walsh
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| Street address |
3 Blackfan St
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (3) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL23423 |
Illumina HiSeq 4000 (Pan troglodytes) |
| GPL27803 |
Illumina HiSeq 4000 (Homo sapiens; Pan troglodytes) |
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| Samples (69)
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| Relations |
| BioProject |
PRJNA766089 |
| SRA |
SRP338623 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE184768_allo-tetraploid_gene_counts.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE184768_chrXdel_gene_counts.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE184768_diploid-and-auto-tetraploid_gene_counts.txt.gz |
618.2 Kb |
(ftp)(http) |
TXT |
| GSE184768_hg38.pt6.gtf.gz |
12.9 Mb |
(ftp)(http) |
GTF |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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