Project description:Among mammals, only primates including human possess a small central retinal region called the fovea, which mediates high acuity vision. As other mammals lack a fovea, molecular bases of its specialized function and dysfunction in retinal diseases remain poorly understood. By analyzing >165,000 single-cell transcriptomes from macaque fovea and peripheral retina, we identified and molecularly characterized >60 major cell types in each region. A few cell types are unique to each region, and there are also substantial differences in proportions and gene expression between corresponding types in the two areas, some of which can be related to functional differences. Comparison of macaque and mouse retinal taxonomies reveals both similarities and differences between species. Many molecular features of macaque retinal cell types are conserved in two other primates, marmosets and humans, and key human retinal disease-associated genes are expressed in specific macaque cell types
Project description:Among mammals, only primates including human possess a small central retinal region called the fovea, which mediates high acuity vision. As other mammals lack a fovea, molecular bases of its specialized function and dysfunction in retinal diseases remain poorly understood. By analyzing >165,000 single-cell transcriptomes from macaque fovea and peripheral retina, we identified and molecularly characterized >60 major cell types in each region. A few cell types are unique to each region, and there are also substantial differences in proportions and gene expression between corresponding types in the two areas, some of which can be related to functional differences. Comparison of macaque and mouse retinal taxonomies reveals both similarities and differences between species. Many molecular features of macaque retinal cell types are conserved in two other primates, marmosets and humans, and key human retinal disease-associated genes are expressed in specific macaque cell types
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.
Project description:Understanding the evolutionary mechanisms underlying expansion and reorganization of the human brain is essential to comprehend the emergence of the cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closely related species (Homo sapiens; human, Pan troglodytes; chimpanzees and Pan paniscus; bonobos) can shed light onto neuronal changes occurring during evolution, the timing of their appearance and the role of evolutionary mechanisms favoring a particular type of cortical organization in humans. The availability of post-mortem brains of endangered primates is limited and often does not represent important species-specific developmental hallmarks. We used induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration in Homo and Pan and early development of cortical pyramidal neurons in humans and chimpanzees after following cells grafted in vivo. We present results suggesting differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos in vitro and in vivo. Additionally, we reveal morphometric and functional differences that are suggestive of heterochronic changes in developing human neurons compared to chimpanzees. This report provides a comprehensive analysis of comparative neural development in closely related hominids. The strategy proposed here lays the groundwork for further comparative analysis between human and non-human primates and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.
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.
Project description:Changes in gene regulation are thought to play an important role in speciation and adaptation, especially in primates. However, we still know relatively little about the mechanisms underlying regulatory evolution. In particular, the extent to which epigenetic modifications underlie gene expression differences between primates is not yet known. Our study focuses on an epigenetic histone modification, H3K4me3, which is thought to promote transcription. To investigate the contribution of H3K4me3 to regulatory differences between species, we collected gene expression data and identified H3K4me3-associated genomic regions in lymphoblastoid cell lines (LCLs) from humans, chimpanzees, and rhesus macaques, using three cell lines from each species. We found strong evidence for conservation of H3K4me3 localization in primates. Moreover, regardless of species, H3K4me3 is consistently enriched near annotated transcription start sites (TSS), and highly expressed genes are more likely than lowly expressed genes to have the histone modification near their TSS. Interestingly, we observed an enrichment of interspecies differences in H3K4me3 at the TSS of genes that are differentially expressed between species. We estimate that as much as 7% of gene expression differences between the LCLs of humans, chimpanzees, and rhesus macaques may be explained, at least in part, by changes in the status of H3K4me3 histone modifications. Our results suggest a modest, yet important role for epigenetic changes in gene expression differences between primates. Examination of H3K4me3 profiles in lymphoblastoid cell lines (LCLs) from three primate species (human, chimpanzee, and rhesus macaque), using 3 samples from each species, compared to a pooled input control from each species. Expression profiling was also done in the same LCL samples.