7 research outputs found
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A panel of induced pluripotent stem cells from chimpanzees: A resource for comparative functional genomics
Comparative genomics studies in primates are restricted due to our limited access to samples. 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 generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To demonstrate 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 withinspecies variation in iPSCs than in somatic cells, indicating 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
Mycobacterial infection induces a specific human innate immune response
International audienceThe innate immune system provides the first response to infection and is now recognized to be partially pathogen-specific. Mycobacterium tuberculosis (MTB) is able to subvert the innate immune response and survive inside macrophages. Curiously, only 5-10% of otherwise healthy individuals infected with MTB develop active tuberculosis (TB). We do not yet understand the genetic basis underlying this individual-specific susceptibility. Moreover, we still do not know which properties of the innate immune response are specific to MTB infection. To identify immune responses that are specific to MTB, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied their transcriptional response. We identified a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. This subset includes genes involved in phagosome maturation, superoxide production, response to vitamin D, macrophage chemotaxis, and sialic acid synthesis. We suggest that genetic variants that affect the function or regulation of these genes should be considered candidate loci for explaining TB susceptibility
A genomic study of the contribution of DNA methylation to regulatory evolution in primates
Trabajo presentado en la Annual meeting of the Society for Molecular Biology and Evolution (SMBE 2015), celebrado en Viena del 12 al 16 de julio de 2015.A long-standing hypothesis is that changes in gene regulation play an important
role in adaptive
evolution, notably in primates. Yet, in spite of the evidence accumulated in the past decade that
regulatory changes contribute to many species-specific adaptations, we still know remarkably little
about the mechanisms of regulatory evolu
tion. In this study we focused on DNA methylation, an
epigenetic mechanism whose contribution to the evolution of gene expression remains unclear.
To interrogate the methylation status of the vast majority of cytosines in the genome, we performed
whole-genome bisulfite conversion followed by high-throughput sequencing across 4 tissues (heart,
kidney, liver and lung) in 3 primate species (human, chimpanzee and macaque). In parallel, we
collected gene expression profiles using RNA-seq from the same tissue sam
ples, allowing us to
perform a high resolution scan for genes and pathways whose regulation evolved under natural
selection.
We integrated these datasets to characterize better the genome features whose methylation status
leads to expression changes, and we developed a statistical model to quantify the proportion of
variation in gene expression levels across tissues and species. We discovered that, in contrast to the
confirmed negative association between gene expression and methylation changes across tissu
es, the correlation was greatly reduced across species. Our study questions the importance of epigenetic
modifications as a mechanism causing regulatory changes and adaptations in primates.N
Integrated analyses of gene expression and genetic association studies in a founder population
A panel of induced pluripotent stem cells from chimpanzees: a resource for comparative functional genomics.
Comparative genomics studies in primates are restricted due to our limited access to samples. 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 generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To demonstrate 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 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