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Modeling human brain evolution using induced pluripotent stem cells: comparative analysis of neuronal development in humans and chimpanzees

ABSTRACT: Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. Here, we use induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration and early development of cortical pyramidal neurons in humans and chimpanzees. In addition, we provide morphological characterization of the early stages of neuronal development in human and chimpanzee transplanted cells, and examine the role of developmental mechanisms previously proposed for the evolutionary expansions of the human brain on the early development of pyramidal neurons in the two species. The strategy proposed here lay down the basis for further comparative analysis between human and non-human primates and opens new avenues for understanding cognitive capability and neurological disease susceptibility differences between species.

ORGANISM(S): Homo sapiens Pan troglodytes

PROVIDER: GSE83638 | GEO | 2016/08/07

SECONDARY ACCESSION(S): PRJNA326545

REPOSITORIES: GEO

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Modeling human brain evolution using induced pluripotent stem cells: comparative analysis of neuronal development in humans and chimpanzees

Project description:Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. Here, we use induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration and early development of cortical pyramidal neurons in humans and chimpanzees. In addition, we provide morphological characterization of the early stages of neuronal development in human and chimpanzee transplanted cells, and examine the role of developmental mechanisms previously proposed for the evolutionary expansions of the human brain on the early development of pyramidal neurons in the two species. The strategy proposed here lay down the basis for further comparative analysis between human and non-human primates and opens new avenues for understanding cognitive capability and neurological disease susceptibility differences between species. PolyA RNA-Seq profiling of neural progenitor cells (NPCs) and neurons differentiated from human and chimpanzee iPSCs.

2016-08-07 | E-GEOD-83638 | biostudies-arrayexpress

Species-specific maturation profiles of human, chimpanzee and bonobo neural cells

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2019-02-14 | GSE124706 | GEO

Widespread conservation of chromatin accessibility and transcription factor binding in human and chimpanzee induced pluripotent stem cells

Project description:Changes in gene regulation have been shown to contribute to phenotypic differences between closely related species, most notably in primates. It is likely that a subset of inter-species regulatory differences can be explained by changes in chromatin accessibility and transcription factor binding, yet there is a paucity of comparative data sets with which to investigate this. Using ATAC-seq, we profiled genome-wide chromatin accessibility in a matched set of 6 human and 6 chimpanzee (Pan troglodytes, our closest living relative) induced pluripotent stem cells from which we have previously collected gene expression data. We examined chromatin accessibility patterns near 20,745 orthologous transcriptions start sites and used a footprinting algorithm to predict transcription factor binding activity in each species. We found that the majority of chromatin accessibility patterns and transcription factor activity are conserved between these two closely related species. Interestingly, interspecies divergence in chromatin accessibility and transcription factor binding in pluripotent cells appear to contribute not to differences in the pluripotent state, but to downstream developmental processes. Put together, our findings suggest that the pluripotent state is extremely stable and potentially subject to stronger evolutionary constraint than other somatic tissues.

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Project description:We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities. Keywords: Age series Human, chimpanzee and rhesus macaque post-mortem brain samples from the cerebellar cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to Affymetrix® Human Gene 1.0 ST arrays. CBC samples.

2011-12-09 | E-GEOD-22569 | biostudies-arrayexpress

Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics (RNA-Seq)

Project description:Comparative studies in primates are extremely restricted because we only have access to a few types of cell lines from non-human apes and to a limited collection of frozen tissues. In order to gain better insight into regulatory processes that underlie variation in complex phenotypes, we must have access to faithful model systems for a wide range of tissues and cell types. To facilitate this, we have generated a panel of 7 fully characterized chimpanzee (Pan troglodytes) induced pluripotent stem cell (iPSC) lines derived from fibroblasts of healthy donors. All lines are free of integration from exogenous reprogramming vectors, can be maintained using standard iPSC culture techniques, and have proliferative and differentiation potential similar to human and mouse lines. To begin demonstrating the utility of comparative iPSC panels, we collected RNA-seq data and methylation profiles from the chimpanzee iPSCs and their corresponding fibroblast precursors, as well as from 7 human iPSCs and their precursors, which were of multiple cell type and population origins. Overall, we observed much less regulatory variation within species in the iPSCs than in the somatic precursors, indicating that the reprogramming process has erased many of the differences observed between somatic cells of different origins. We identified 4,918 differentially expressed genes and 1,986 differentially methylated regions between iPSCs of the two species, many of which are novel inter-species differences and not observed between the somatic cells of the two species. Our panel will help realize the potential of iPSCs, and in combination with genomic technologies, transform studies of comparative evolution in primates. We obtained RNA sequencing and methylation profiles from 7 chimpanzee iPSCs and the fibroblasts used to generate them, as well as 7 human iPSCs and the LCLs and fibroblasts used to generate them.

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Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics (methylation array)

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2014-09-11 | E-GEOD-61342 | biostudies-arrayexpress

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Molecular and cellular changes underlying evolutionary specializations of primate dorsolateral prefrontal cortex

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