A panel of induced pluripotent stem cells from chimpanzees: a resource for comparative functional genomics

Author:

Gallego Romero Irene1ORCID,Pavlovic Bryan J1,Hernando-Herraez Irene2,Zhou Xiang3,Ward Michelle C1,Banovich Nicholas E1,Kagan Courtney L1,Burnett Jonathan E1,Huang Constance H1,Mitrano Amy1,Chavarria Claudia I1,Friedrich Ben-Nun Inbar4,Li Yingchun56,Sabatini Karen467,Leonardo Trevor R467,Parast Mana56,Marques-Bonet Tomas28,Laurent Louise C67,Loring Jeanne F4,Gilad Yoav1

Affiliation:

1. Department of Human Genetics, University of Chicago, Chicago, United States

2. Institut de Biologia Evolutiva (CSIC/UPF), Barcelona, Spain

3. Department of Biostatistics, University of Michigan, Ann Arbor, United States

4. Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States

5. Department of Pathology, University of California San Diego, San Diego, United States

6. Sanford Consortium for Regenerative Medicine, La Jolla, United States

7. Department of Reproductive Medicine, University of California San Diego, San Diego, United States

8. Centro Nacional de Análisis Genómico (CNAG-CRG), Barcelona, Spain

Abstract

Comparative genomics studies in primates are restricted due to our limited access to samples. In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates, we must have access to faithful model systems for a wide range of cell types. To facilitate this, we generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To demonstrate the utility of comparative iPSC panels, we collected RNA-sequencing and DNA methylation data from the chimpanzee iPSCs and the corresponding fibroblast lines, as well as from 7 human iPSCs and their source lines, which encompass multiple populations and cell types. We observe much less within-species variation in iPSCs than in somatic cells, indicating the reprogramming process erases many inter-individual differences. The low within-species regulatory variation in iPSCs allowed us to identify many novel inter-species regulatory differences of small magnitude.

Funder

Wellcome Trust

National Institutes of Health (NIH)

California Institute for Regenerative Medicine (CIRM)

European Research Council (ERC)

Ministerio de Economía y Competitividad

University of California, San Diego, Department of Reproductive Medicine

Generalitat de Catalunya

EMBO

National Center for Advancing Translational Sciences

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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