title: Novel tools, classic techniques: evolutionary studies using primate pluripotent stem cells.
abstract: Recent applications of genomic tools on the analysis of alterations unique to our species coupled with a growing number of neuroanatomical studies across primates provide an unprecedented opportunity to compile different levels of human brain evolution into a complex whole. Applications of induced pluripotent stem cell (iPSC) technology, capable of reprogramming somatic tissue of different species and generating species-specific neuronal phenotypes, for the first time offer an opportunity to test specific evolutionary hypotheses in a field of inquiry that has been long plagued by the limited availability of research specimens. In this review, we will focus specifically on the experimental role of iPSC technology as applied to the analysis of neocortical pyramidal neurons. Pyramidal neurons emerge as particularly suitable for testing evolutionary scenarios, since they form the most common morphological class of neurons in the cortex, display morphological variations across different cortical areas and cortical layers that appear species-specific, and express unique molecular signatures. Human and nonhuman primate iPSC-derived neurons may represent a unique biological resource to elucidate the phenotypic differences between humans and other hominids. As the typical morphology of pyramidal neurons tends to be compromised in neurological disorders, application of iPSC technology to the analysis of pyramidal neurons could not only bring new insights into human adaptation but also offer opportunities to link biomedical research with studies of the origins of the human species.
authors.affiliation: Department of Anthropology; School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, University of California San Diego.
authors.forename: Branka
authors.initials: B
authors.lastname: Hrvoj-Mihic
authors.affiliation: Laboratory of Genetics (MCNM, FHG), The Salk Institute for Biological Studies.
authors.forename: Maria C N
authors.initials: MC
authors.lastname: Marchetto
authors.affiliation: Laboratory of Genetics (MCNM, FHG), The Salk Institute for Biological Studies; Center for Academic Research and Training in Anthropogeny.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.affiliation: Department of Anthropology; Center for Academic Research and Training in Anthropogeny; Neuroscience Graduate Program, University of California San Diego, La Jolla, California.
authors.forename: Katerina
authors.initials: K
authors.lastname: Semendeferi
authors.affiliation: School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, University of California San Diego; Center for Academic Research and Training in Anthropogeny; Neuroscience Graduate Program, University of California San Diego, La Jolla, California. Electronic address: muotri@ucsd.edu.
authors.forename: Alysson R
authors.initials: AR
authors.lastname: Muotri
mesh_terms: D000818:Animals; D005075:Biological Evolution; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000473:pathology; D009422:Nervous System Diseases / Q000473:pathology / Q000503:physiopathology; D055495:Neurogenesis; D010641:Phenotype; D011323:Primates; D017966:Pyramidal Cells / Q000166:cytology / Q000473:pathology
keywords: Brain development; evolutionary model; induced pluripotent stem cells