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

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.DOI: http://dx.doi.org/10.7554/eLife.07103.001

Reorganization of 3D Genome Structure May Contribute to Gene Regulatory Evolution in Primates

“…We performed in situ Hi-C as previously described [45] on a sex-balanced panel of four human and four chimpanzee integration-free iPSC lines that were previously generated and quality-checked by the Gilad lab [50]. Using HiCUP [51] and HOMER [52] (see Methods), we obtained genome-wide Hi-C contact maps at 10 kb resolution for all eight individuals, with each map containing approximately one billion sequencing reads.…”

“…As described previously, the Gilad lab has derived panels of both human and chimpanzee iPSCs via episomal reprogramming [50]. We collected human fibroblasts with informed consent obtained from all human participants under University of Chicago IRB protocol 11-0524,.…”

Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution

“…Indeed, genetic variation within the human population coupled with quantitative epigenomic approaches can be leveraged to link sequence changes to chromatin state divergence, both locally and distally within interacting chromosomal regions, providing an avenue for an interpretation of GWAS studies and future investigations of mechanisms underlying disease traits (Grubert et al, 2015; Waszak et al, 2015). Similarly, evidence has accumulated that enhancer sequence changes mediate morphological divergence between species, and ‘cellular anthropology’ approaches utilizing pluripotent stem cells from great apes have enabled investigation of recent hominid cis-regulatory landscape evolution in developmentally and evolutionary relevant cell types (Prescott et al, 2015)(Gallego Romero et al, 2015). Further understanding of the contribution of enhancer sequence variation to human disease susceptibility, normal range variation and evolutionary innovation will likely soon come from human genetics and follow-up functional studies in cells and model organisms.…”

Evolution of the Human Nervous System Function, Structure, and Development

“…Developments in iPSC research provide another method for evolutionary and functional analyses (Gallego Romero et al, 2015; Hrvoj-Mihic et al, 2014; Wunderlich et al, 2014). Methods for generating iPSCs and directing their differentiation into specific human neural cell types and cell culture systems, including organoids, have provided much-needed tools for comparative studies of neurodevelopment in humans and NHPs (Gallego Romero et al, 2015; Hrvoj-Mihic et al, 2014; Otani et al, 2016; Prescott et al, 2015; Wunderlich et al, 2014).…”

“…Methods for generating iPSCs and directing their differentiation into specific human neural cell types and cell culture systems, including organoids, have provided much-needed tools for comparative studies of neurodevelopment in humans and NHPs (Gallego Romero et al, 2015; Hrvoj-Mihic et al, 2014; Otani et al, 2016; Prescott et al, 2015; Wunderlich et al, 2014). Recently, Prescott et al (2015) differentiated cranial neural crest cells from iPSCs derived from human and chimpanzee fibroblasts to study the evolution of human craniofacial morphology.…”