Primate iPS cells as tools for evolutionary analyses
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ABSTRACT:
PROVIDER: PRJNA218873 | ENA |
REPOSITORIES: ENA
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Project description:Induced pluripotent stem cells (iPSCs) are regarded as a central tool to understand human biology in health and disease. Similarly, iPSCs from closely related species should be a central tool to understand human evolution and to identify conserved and variable patterns of iPSC disease models. Here, we have generated human, gorilla, bonobo and cynomolgus monkey iPSCs. We show that these cells are well comparable in their differentiation potential and generally similar to human, cynomolgus and rhesus monkey embryonic stem cells (ESCs). RNA sequencing reveals that expression differences among clones, individuals and stem cell type are all of very similar magnitude within a species. In contrast, expression differences between closely related primate species are three times larger and most genes show significant expression differences among the analysed species. However, pseudogenes differ more than twice as much, suggesting that evolution of expression levels in primate stem cells is rapid, but constrained. These patterns in pluripotent stem cells are comparable to those found in other tissues except testis. Hence, primate iPSCs reveal insights into general primate gene expression evolution and should provide a rich source to identify conserved and species-specific gene expression patterns for cellular phenotypes. Contributors: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany We used expression profiling to characterize five gorilla, two bonobo and three macaque iPS clones as well as three iPS clones from two human individuals, three human embryonic stem (ES) cell lines and three macaque ES cell lines. We generated tagged RNA-Seq libraries from these 19 samples including four technical replicates (23 samples). Over 100 million single end reads were generated on the Illumina platform.
2014-02-19 | E-GEOD-50781 | biostudies-arrayexpress
Project description:Induced pluripotent stem cells (iPSCs) are regarded as a central tool to understand human biology in health and disease. Similarly, iPSCs from closely related species should be a central tool to understand human evolution and to identify conserved and variable patterns of iPSC disease models. Here, we have generated human, gorilla, bonobo and cynomolgus monkey iPSCs. We show that these cells are well comparable in their differentiation potential and generally similar to human, cynomolgus and rhesus monkey embryonic stem cells (ESCs). RNA sequencing reveals that expression differences among clones, individuals and stem cell type are all of very similar magnitude within a species. In contrast, expression differences between closely related primate species are three times larger and most genes show significant expression differences among the analysed species. However, pseudogenes differ more than twice as much, suggesting that evolution of expression levels in primate stem cells is rapid, but constrained. These patterns in pluripotent stem cells are comparable to those found in other tissues except testis. Hence, primate iPSCs reveal insights into general primate gene expression evolution and should provide a rich source to identify conserved and species-specific gene expression patterns for cellular phenotypes. Contributors: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany
2014-02-19 | GSE50781 | GEO
Project description:Messenger RNA secondary structure is critical to all aspects of post-transcriptional regulation. However, the global regulatory and evolutionary significance of mRNA secondary structure remains largely illusive. Here, we describe a transcriptome-wide analysis of RNA secondary structure in humans and two non-human primates, based on a high-throughput, nuclease-mediated, structure mapping approach. Using this methodology, we uncover global patterns of mRNA secondary structure, which we find to be conserved through primate evolution. We provide evidence for secondary structure-based regulatory pathways, which impact on gene expression through associations with translational machinery and RNA-binding proteins, including components of the microprocessor complex. Our results lend support to an unexpected, conserved mechanism by which highly structured regions of mRNAs serve as processing sites for small RNAs, resulting in subsequent turnover. Global mRNA secondary structure analysis in primate transcriptomes using high-throughput, nuclease-mediated, structure mappinng approaches of dsRNA-seq and ssRNA-seq, also with polyA+ mRNA-seq, smRNA-seq (small RNA), and genome-wide mapping of uncapped and cleaved transcripts (GMUCT); these NGS-seq experiments were carried out in three primate brains as well as three different cell lines, both in in vitro and in vivo.
2017-05-01 | E-GEOD-57295 | biostudies-arrayexpress
Project description:The cellular and genetic mechanism underlying the human-specific features of cortex development remains unclear. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility of the developing macaque and mouse prefrontal cortex, and conducted evolutionary analyses with the published complementary human data. The cortex cell type composition shows an overall conservation across species. We found the human neural progenitors show extensive transcriptional rewiring in the growth factor and extracellular matrix pathways. Expression of the human-specific progenitor marker ITGA2 in the cortex of fetal mouse promotes progenitor proliferation and an increased upper-layer neuron proportion. We demonstrate that these transcriptional divergences are primarily driven by the activity changes of the distal regulatory elements in the genome. Markedly, the chromatin regions with human-gained accessibility enrich the human-fixed sequence changes, as well as sequence polymorphisms associated with intelligence and neuropsychiatric disorders. Our results uncover evolutionary innovations in neural progenitors and gene regulatory mechanism during primate cortex evolution.
2024-06-09 | GSE241429 | GEO
Project description:As ontogeny does not recapitulate phylogeny and little developmental restraint exists prior to gastrulation, early mammalian development differs significantly between species. A prime example is the temporal difference in the first emergence of extra-embryonic mesenchymal cells (ExMC) between mouse and human. Here, we report a fast and efficient in vitro cell model of human ExMC formation from induced pluripotent stem cells. This ExMC emerges from the apparent late blastocystic trophoblast. We define HAND1 as an essential regulator of ExMC specification, with HAND1 null cells reverting to the trophoblast lineage. Regulatory phenotyping defines primary target genes of, and primate-specific genomic regions bound by, HAND1. These data emphasize the nascent evolutionary innovation in early development relevant to human health but, through pleiotropy, also to later in life human biology. The novel findings that trophectoderm is a source of ExMC lineage and how recently evolved young transposable elements regulate this process emphasize the evolutionary novelties of our model to explore the primate embryogenesis.
2024-12-02 | GSE220840 | GEO
Project description:As ontogeny does not recapitulate phylogeny and little developmental restraint exists prior to gastrulation, early mammalian development differs significantly between species. A prime example is the temporal difference in the first emergence of extra-embryonic mesenchymal cells (ExMC) between mouse and human. Here, we report a fast and efficient in vitro cell model of human ExMC formation from induced pluripotent stem cells. This ExMC emerges from the apparent late blastocystic trophoblast. We define HAND1 as an essential regulator of ExMC specification, with HAND1 null cells reverting to the trophoblast lineage. Regulatory phenotyping defines primary target genes of, and primate-specific genomic regions bound by, HAND1. These data emphasize the nascent evolutionary innovation in early development relevant to human health but, through pleiotropy, also to later in life human biology. The novel findings that trophectoderm is a source of ExMC lineage and how recently evolved young transposable elements regulate this process emphasize the evolutionary novelties of our model to explore the primate embryogenesis.
2024-12-02 | GSE219291 | GEO
Project description:As ontogeny does not recapitulate phylogeny and little developmental restraint exists prior to gastrulation, early mammalian development differs significantly between species. A prime example is the temporal difference in the first emergence of extra-embryonic mesenchymal cells (ExMC) between mouse and human. Here, we report a fast and efficient in vitro cell model of human ExMC formation from induced pluripotent stem cells. This ExMC emerges from the apparent late blastocystic trophoblast. We define HAND1 as an essential regulator of ExMC specification, with HAND1 null cells reverting to the trophoblast lineage. Regulatory phenotyping defines primary target genes of, and primate-specific genomic regions bound by, HAND1. These data emphasize the nascent evolutionary innovation in early development relevant to human health but, through pleiotropy, also to later in life human biology. The novel findings that trophectoderm is a source of ExMC lineage and how recently evolved young transposable elements regulate this process emphasize the evolutionary novelties of our model to explore the primate embryogenesis.
2024-12-02 | GSE219290 | GEO
Project description:Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution and immune response. While the generation of human induced PS (iPS) cell-derived myogenic progenitors is well established, there has been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage. Here we report the generation of three independent Macaca fascicularis iPS cell lines and their myogenic differentiation using PAX7 conditional expression. Whole transcriptome analysis confirmed the successful sequential induction of mesoderm, paraxial mesoderm, and myogenic lineages. NHP myogenic progenitors efficiently gave rise to myotubes under appropriate in vitro differentiation conditions and engrafted in vivo into TA muscles of NSG and FKRP-NSG mice. Lastly, we explored the pre-clinical potential of these NHP myogenic progenitors in a single wild-type NHP recipient, demonstrating engraftment and characterizing the interaction with the host immune response. These studies establish an NHP model system in which to study iPS cell-derived myogenic progenitors.
2023-05-03 | GSE228567 | GEO
Project description:Messenger RNA secondary structure is critical to all aspects of post-transcriptional regulation. However, the global regulatory and evolutionary significance of mRNA secondary structure remains largely illusive. Here, we describe a transcriptome-wide analysis of RNA secondary structure in humans and two non-human primates, based on a high-throughput, nuclease-mediated, structure mapping approach. Using this methodology, we uncover global patterns of mRNA secondary structure, which we find to be conserved through primate evolution. We provide evidence for secondary structure-based regulatory pathways, which impact on gene expression through associations with translational machinery and RNA-binding proteins, including components of the microprocessor complex. Our results lend support to an unexpected, conserved mechanism by which highly structured regions of mRNAs serve as processing sites for small RNAs, resulting in subsequent turnover.
2017-05-01 | GSE57295 | GEO
Project description:The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. Here, we assessed over 600,000 single-nucleus transcriptomes from human, chimpanzee, macaque, and marmoset dlPFC. While major subclasses of transcriptomically-defined cell subtypes are conserved, we detected several subtypes only in some species and substantial species-specific molecular differences across homologous neuronal, glial and non-neural subtypes. The latter are exemplified by human-specific switching between translation of the neuropeptide somatostatin (SST) and tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine production, in certain interneurons, and also by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer-4 granular neurons. We generated a comprehensive transcriptomic and cellular survey of dlPFC evolution in anthropoid primates.
2022-08-25 | GSE206994 | GEO