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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (bulk RNA-seq)

ABSTRACT: Here we characterize microglia transcriptional program across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to human, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, while humans express significant microglia heterogeneity. In addition, we observed notable differences in complement, phagocytic and several critical signaling pathways that are enriched with susceptibility genes to brain disorders, including Alzheimer’s and Parkinson’s disease in microglia of common animal models as compared to human. Our study provides an essential resource of conserved and divergent microglia pathways across evolution with important implications for future development of microglia-based therapies in humans.

ORGANISM(S): Mesocricetus auratus Callithrix jacchus Mus musculus Rattus norvegicus Danio rerio Macaca fascicularis Gallus gallus Homo sapiens Ovis aries

PROVIDER: GSE134706 | GEO | 2019/12/12

REPOSITORIES: GEO

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (scRNA-seq)

Project description:Here we characterize microglia transcriptional program across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to human, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, while humans express significant microglia heterogeneity. In addition, we observed notable differences in complement, phagocytic and several critical signaling pathways that are enriched with susceptibility genes to brain disorders, including Alzheimer’s and Parkinson’s disease in microglia of common animal models as compared to human. Our study provides an essential resource of conserved and divergent microglia pathways across evolution with important implications for future development of microglia-based therapies in humans.

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (scRNA-seq)

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Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-12 | GSE134707 | GEO

A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees

Project description:Despite anatomical similarities, there are differences in susceptibility to cardiovascular disease (CVD) between primates; humans are prone to myocardial ischemia, while chimpanzees are prone to myocardial fibrosis. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) allow for direct inter-species comparisons of the gene regulatory response to CVD-relevant perturbations such as oxygen deprivation, a consequence of ischemia. To gain insight into the evolution of disease susceptibility, we characterized gene expression levels in iPSC-CMs in humans and chimpanzees, before and after hypoxia and re-oxygenation. The transcriptional response to hypoxia is generally conserved across species, yet we were able to identify hundreds of species-specific regulatory responses including in genes previously associated with CVD. The 1,920 genes that respond to hypoxia in both species are enriched for loss-of-function intolerant genes; but are depleted for expression quantitative trait loci and cardiovascular-related genes. Our results indicate that response to hypoxic stress is highly conserved in humans and chimpanzees.

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A conserved transcriptional program for MAIT cells across mammalian evolution [Hsapiens_thymus_NKT]

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