Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Comparative Assessment of iPSC Derived Cardiomyocytes with Heart Tissues in Humans and Chimpanzees

ABSTRACT: To study regulatory differences between species, the field of comparative primate genomics has used several approaches, including the use of post mortem frozen tissues, cell lines, and model organisms. However, there are limited quality cell lines from primates and post-mortem tissues cannot be staged, are not amenable to experimental perturbations and are often subject to high environmental variances. Inducible pluripotent stem cells (iPSCs) are an attractive system to study primate biology in a comparative context. However, the fidelity of iPSC derived cell types to primary tissues needs to be assayed in a comparative primate context before the utility of iPSCs can be fully realized for comparative genomics. In order to comprehensively benchmark the performance of iPSC model systems in a comparative framework, we collected RNA-sequencing from primary adult heart tissue and iPSC derived cardiomyocytes from multiple human and chimpanzee individuals. We identified the optimal parameters of iPSC differentiation into cardiomyocytes that minimized differences between each species and their respective adult tissue counterparts in a balanced manner across species. We found that iPSC derived cardiomyocytes are able to recapitulate 50% of the interspecies gene expression differences identified between human and chimpanzee in primary post mortem heart tissues. Furthermore, we determined that cultured cardiomyocytes appear more similar to adult hearts than any other single tissue in their ability to recapitulate differences in gene regulation between human and chimpanzee.

ORGANISM(S): Homo sapiens Pan troglodytes

PROVIDER: GSE110471 | GEO | 2018/08/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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.

2014-09-10 | E-GEOD-60996 | biostudies-arrayexpress

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

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 realise 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.

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

Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics [ChIP-Seq]

Project description:Comparative genomics studies in primates are extremely restricted due to our limited access to samples from non-human apes. In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates, we must have access to faithful model systems for a wide range of cell types. To facilitate this, we have generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To begin demonstrating the utility of comparative iPSC panels, we collected RNA-sequencing and DNA methylation data from the chimpanzee iPSCs and the corresponding fibroblast lines, as well as from 7 human iPSCs and their source lines, which encompass multiple populations and cell types. We observe much less within-species variation in iPSCs than in somatic cells, indicating that the reprogramming process erases many inter-individual differences. The low within-species regulatory variation in iPSCs allowed us to identify many novel inter-species regulatory differences of small magnitude. We used ChIP-seq to characterize the genome-wide distribution of two types of histone modifications (H3K27me3 and H3K27ac) in three of our chimpanzee iPSCs and compared them to histone modification data from three human iPSC lines from the Roadmap Epigenomics project:

2015-06-17 | E-GEOD-69919 | biostudies-arrayexpress

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

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 realise the potential of iPSCs, and in combination with genomic technologies, transform studies of comparative evolution in primates.

2014-09-11 | GSE61342 | GEO

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

2014-09-10 | GSE60996 | GEO

Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics [ChIP-Seq]

2015-06-17 | GSE69919 | GEO

A Genome-wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues

Project description:It has long been hypothesized that changes in gene regulation have played an important role in primate evolution. However, despite the wealth of comparative gene expression data, there are still only few studies that focus on the mechanisms underlying inter-primate differences in gene regulation. In particular, we know relatively little about the degree to which changes in epigenetic profiles might explain differences in gene expression levels between primates. To this end, we studied DNA methylation and gene expression levels in livers, hearts, and kidneys from multiple humans and chimpanzees. Genome wide DNA methylation profiling of heart, kidney, and liver samples from humans and chimpanzees. The Illumina Infinium 27K Human DNA Methylation BeadChip v1.2 was used to compare DNA methylation profiles across approximately 10,575 CpG sites in human and chimpanzee tissue samples. Samples included 6 human livers, 6 human kidneys, 6 human heart, 6 chimpanzee livers, 6 chimpanzee kidneys, and 6 chimpanzee hearts. Two techical replicates of bisulfite converted DNA from each of the 36 samples was hybridized to the Illumina HumanMethylation27 Beadchip. We limited our analysis to the 10,575 probes that were a perfect sequence match to both the human and chimpanzee genomes and which were associated with genes for which we had previously collected expression measurements across the three tissues.

2011-02-25 | E-GEOD-26033 | biostudies-arrayexpress

Primate cell fusion disentangles gene regulatory divergence in neural development

Project description:Among primates, humans display a unique trajectory of development responsible for the many traits specific to our species. However, the inaccessibility of human and chimpanzee primary tissues has limited our ability to study human evolution. Comparative in vitro approaches using primate-derived induced pluripotent stem cells have begun to reveal species differences on the cellular and molecular levels. In particular, brain organoids have emerged as a promising platform to study primate neural development in vitro, although cross-species comparisons of organoids are complicated by differences in developmental timing and variability of differentiation. Here, we developed a new platform to address these limitations. We first generated a panel of tetraploid hybrid stem cells by fusing human and chimpanzee induced pluripotent stem cells. We next applied this approach to study species divergence in cerebral cortical development by differentiating them into neural organoids. We found that hybrid organoids provide a controlled system for disentangling cis- and trans-acting gene expression divergence across cell types and developmental stages, revealing a signature of selection on astrocyte-related genes. In addition, we identified an up-regulation of human somatostatin receptor 2 (SSTR2), which regulates neuronal calcium signaling and is associated with neuropsychiatric disorders. We discovered a human-specific response to modulation of SSTR2 function in cortical neurons, underscoring the potential of this unique platform to reveal the molecular basis of human evolution.

2020-11-17 | GSE144825 | GEO

Functional abnormalities in iPSC-CMs generated from titin-mutated patients

Project description:Dilated cardiomyopathy (DCM), a myocardial disorder that can result in progressive heart failure and arrhythmias, is defined by ventricular chamber enlargement and dilatation, and systolic dysfunction. To decipher the basis for the cardiac pathology in titin-mutated patients, we investigated the hypothesis that induced Pluripotent Stem Cell (iPSC)- derived cardiomyocytes (iPSC-CM) generated from patients, recapitulate the disease phenotype.Our findings show that the mutated cardiomyocytes from DCM patients recapitulate abnormalities of the inherited cardiomyopathies.

2019-04-12 | PXD010513 | Pride

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [Dnase-seq]

Project description:The human genome shares a remarkable amount of genomic sequence with our closest living primate relatives. Researchers have long sought to understand what regions of the genome are responsible for unique species-specific traits. Previous studies have shown that many genes are differentially expressed between species, but the regulatory elements contributing to these differences are largely unknown. Here we report a genome-wide comparison of active gene regulatory elements in human, chimpanzee, and macaque, and we identify hundreds of regulatory elements that have been gained or lost in the human or chimpanzee genomes since their evolutionary divergence. These elements contain evidence of natural selection and correlate with species-specific changes in gene expression. Polymorphic DNA bases in transcription factor motifs that we found in these regulatory elements may be responsible for the varied biological functions across species. This study directly links phenotypic and transcriptional differences between species with changes in chromatin structure. One biological replicate was analyzed for each of the 15 primate samples using DNase-seq.

2014-02-13 | E-GEOD-54907 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data