@article{TEXTUAL,
      recid = {6310},
      author = {Housman, Genevieve and Briscoe, Emilie and Gilad, Yoav},
      title = {Evolutionary insights into primate skeletal gene  regulation using a comparative cell culture model},
      journal = {PLOS Genetics},
      address = {2022-03-09},
      number = {TEXTUAL},
      abstract = {The evolution of complex skeletal traits in primates was  likely influenced by both genetic and environmental  factors. Because skeletal tissues are notoriously  challenging to study using functional genomic approaches,  they remain poorly characterized even in humans, let alone  across multiple species. The challenges involved in  obtaining functional genomic data from the skeleton,  combined with the difficulty of obtaining such tissues from  nonhuman apes, motivated us to consider an alternative in  vitro system with which to comparatively study gene  regulation in skeletal cell types. Specifically, we  differentiated six human (Homo sapiens) and six chimpanzee  (Pan troglodytes) induced pluripotent stem cell lines  (iPSCs) into mesenchymal stem cells (MSCs) and subsequently  into osteogenic cells (bone cells). We validated  differentiation using standard methods and collected  single-cell RNA sequencing data from over 100,000 cells  across multiple samples and replicates at each stage of  differentiation. While most genes that we examined display  conserved patterns of expression across species, hundreds  of genes are differentially expressed (DE) between humans  and chimpanzees within and across stages of osteogenic  differentiation. Some of these interspecific DE genes show  functional enrichments relevant in skeletal tissue trait  development. Moreover, topic modeling indicates that  interspecific gene programs become more pronounced as cells  mature. Overall, we propose that this in vitro model can be  used to identify interspecific regulatory differences that  may have contributed to skeletal trait differences between  species.},
      url = {http://knowledge.uchicago.edu/record/6310},
}