Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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. PolyA RNA-Seq profiling of neural progenitor cells (NPCs) and neurons differentiated from human and chimpanzee iPSCs.

ORGANISM(S): Pan troglodytes

SUBMITTER: Inigo Narvaiza

PROVIDER: E-GEOD-83638 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility.

Nuttle Xander X Giannuzzi Giuliana G Duyzend Michael H MH Schraiber Joshua G JG Narvaiza Iñigo I Sudmant Peter H PH Penn Osnat O Chiatante Giorgia G Malig Maika M Huddleston John J Benner Chris C Camponeschi Francesca F Ciofi-Baffoni Simone S Stessman Holly A F HA Marchetto Maria C N MC Denman Laura L Harshman Lana L Baker Carl C Raja Archana A Penewit Kelsi K Janke Nicolette N Tang W Joyce WJ Ventura Mario M Banci Lucia L Antonacci Francesca F Akey Joshua M JM Amemiya Chris T CT Gage Fred H FH Reymond Alexandre A Eichler Evan E EE

Nature 20160803 7615

Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates, including more recently the genomes of archaic hominins. Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism and is mediated by a complex set of segmental duplications, many of which ar ...[more]

PMID: 27487209

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Project description:Understanding cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic comprehension of the evolution and diversity of our own species. Until now, preserved tissues have been the main source of most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behavior, are not amenable to genetic manipulation and do not allow translation of observed differences into phenotypical divergence. We hypothesized that induced pluripotent stem cells (iPSCs) could provide a unique biological resource to elucidate relevant phenotypical differences between human and the great apes and that those differences could have potential adaptation and speciation value. Here, we describe the generation and initial characterization of iPSCs from chimpanzees and bonobos as novel tools to explore our most recent evolution. Comparative gene expression analysis of human and NHP iPSCs revealed differences in regulation of Long Interspersed Nuclear Element (LINE-1 or L1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. We observed decreased levels of L1 restricting factors APOBEC3B (A3B)7 and PIWIL28 in NHP iPSCs which was correlated with increased human and chimpanzee L1 mobility and endogenous L1 mRNA levels. Moreover, results from manipulation of A3B and PIWIL2 levels in iPSCs suggested a causal inverse relationship between levels of these proteins and L1 activity. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPSCs in culture and may have also occurred in the germline during primate evolution. We propose that differences in L1 mobility may have differentially shaped the genomes of humans and NHPs and could have had an adaptive significance. polyA RNA-Seq profiling of iPS cells from human, chimpanzee, and bonobo, and small RNA-Seq profiling of human iPS cells.

Project description:The chimpanzee is the only model other than man for investigating the pathogenesis of viral hepatitis types A through E. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host response to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), was compared in multiple experimentally-infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. The comparison utilized a permutational t-test-based analysis of selected time points. More specifically, baseline samples were compared with post-inoculation samples that were strategically chosen based on their relationship to viremia, and probe sequences were aligned to the human and chimpanzee genome sequences to assess their relative sensitivity for detecting differentially expressed genes. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust than the response to HEV infection. Three chimpanzees were inoculated intravenously with the hepatitis C virus: chimp 1628 was infected with < 100 infectious doses (ID) of the H77 strain (genotype 1a) (30); chimp 1417 was infected with an unknown titer, in serum, of the HC-J6 strain (genotype 2a) (31); chimp 1422 was infected with an unknown titer, in serum, of the T.N. strain (genotype 1a) (35). Four chimpanzees (CH1616, CH1618, CH1374 and CH1375) were inoculated intravenously with 0.5 ml of the HEV SAR55 strain (genotype 1) at approximately 10^6 ID. Grouping of the biological replicates was based on viremia: groups consisted of the first positive week (and the second positive week for HCV), the peak positive week, the last positive week, the first negative week and the fourth negative week. There were 3 biological replicates for HCV. The 4 replicates for HEV were both biological and technical. For chimp 1417, 7 samples were taken between weeks 0 and 17. For chimp 1422, 8 samples were taken between weeks 0 and 13. For chimp 1628, 8 samples were taken between weeks 0 and 19. For chimp 1374, 6 samples were taken between weeks 0 and 8. For chimp 1375, 4 samples were taken between weeks 0 and 8. For chimp 1616, 5 samples were taken between weeks 0 and 7. For chimp 1618, 6 samples were taken between weeks 0 and 8. Normalized probe set level data not provided for individual Sample records. Processed data is available on Series record.

Dataset Information

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

Publications

Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility.

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