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A comparative study of endoderm differentiation in humans and chimpanzees

Lauren E. Blake, Samantha M. Thomas, John D. Blischak, Chiaowen Joyce Hsiao, Claudia Chavarria, Marsha Myrthil, Yoav Gilad, Bryan J. Pavlovic
doi: https://doi.org/10.1101/135442
Lauren E. Blake
1University of Chicago, Department of Human Genetics, Chicago, IL
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Samantha M. Thomas
1University of Chicago, Department of Human Genetics, Chicago, IL
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John D. Blischak
1University of Chicago, Department of Human Genetics, Chicago, IL
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Chiaowen Joyce Hsiao
1University of Chicago, Department of Human Genetics, Chicago, IL
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Claudia Chavarria
1University of Chicago, Department of Human Genetics, Chicago, IL
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Marsha Myrthil
1University of Chicago, Department of Human Genetics, Chicago, IL
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Yoav Gilad
1University of Chicago, Department of Human Genetics, Chicago, IL
2University of Chicago, Department of Medicine, Chicago, IL
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  • For correspondence: gilad@uchicago.edu
Bryan J. Pavlovic
1University of Chicago, Department of Human Genetics, Chicago, IL
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Abstract

There is substantial interest in the evolutionary forces that shaped the regulatory framework that is established in early human development. Progress in this area has been slow because it is difficult to obtain relevant biological samples. Inducible pluripotent stem cells (iPSCs) provide the ability to establish in vitro models of early human and non-human primate developmental stages. Using matched iPSC panels from humans and chimpanzees, we comparatively characterized gene regulatory changes through a four-day timecourse differentiation of iPSCs (day 0) into primary streak (day 1), endoderm progenitors (day 2), and definitive endoderm (day 3). As might be expected, we found that differentiation stage is the major driver of variation in gene expression levels, followed by species. We identified thousands of differentially expressed genes between humans and chimpanzees in each differentiation stage. Yet, when we considered gene-specific dynamic regulatory trajectories throughout the timecourse, we found that 75‥ of genes, including nearly all known endoderm developmental markers, have similar trajectories in the two species. Interestingly, we observed a marked reduction of both intra-and inter-species variation in gene expression levels in primitive streak samples compared to the iPSCs, with a recovery of regulatory variation in endoderm progenitors. The reduction of variation in gene expression levels at a specific developmental stage, paired with overall high degree of conservation of temporal gene regulation, is consistent with the dynamics of developmental canalization. Overall, we conclude that endoderm development in iPSC-based models are highly conserved and canalized between humans and our closest evolutionary relative.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 09, 2017.
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A comparative study of endoderm differentiation in humans and chimpanzees
Lauren E. Blake, Samantha M. Thomas, John D. Blischak, Chiaowen Joyce Hsiao, Claudia Chavarria, Marsha Myrthil, Yoav Gilad, Bryan J. Pavlovic
bioRxiv 135442; doi: https://doi.org/10.1101/135442
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A comparative study of endoderm differentiation in humans and chimpanzees
Lauren E. Blake, Samantha M. Thomas, John D. Blischak, Chiaowen Joyce Hsiao, Claudia Chavarria, Marsha Myrthil, Yoav Gilad, Bryan J. Pavlovic
bioRxiv 135442; doi: https://doi.org/10.1101/135442

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