Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity
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ABSTRACT:
ORGANISM(S): Pan troglodytes Homo sapiens Papio anubis Macaca mulatta
PROVIDER: GSE155918 | GEO | 2020/08/09
REPOSITORIES: GEO
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Project description:The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that the differentiation of neuroepithelial cells to neurogenic radial glia is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition. Temporally resolved RNA-seq from human and gorilla organoids reveals differences in gene expression patterns associated with cell morphogenesis, and in particular highlight ZEB2, a known regulator of epithelial-mesenchymal transition and cell shape. We show, through loss- and gain-of-function experiments, that ZEB2 promotes the progression of neuroepithelial differentiation, and its ectopic overexpression in human is sufficient to trigger a premature transition. By mimicking the nonhuman ape expression of this human evolution gene, we are able to force the acquisition of nonhuman ape architecture in human organoids, establishing for the first time, an instructive role of neuroepithelial cell shape in human brain expansion.
2020-07-06 | GSE153076 | GEO
Project description:IL-4 drives expansion of Th2 cells that cause generation of alternatively activated macrophages (AAMs). Filarial infections are established early in life, induce increased IL-4 production are co-endemic with tuberculosis (TB). We sought to understand, therefore, how mycobacteria are handled in the context of IL-4-induced AAM. Comparing IL-4 generated in vitro monocyte derived human AAMs to LPS and IFN-γ generated classically macrophages (CAMs), both infected with mycobacteria (BCG), we demonstrated increased early BCG uptake and increased IL-10 production in AAMs compared to CAMs. We further demonstrated that increased IL-10 production is mediated by upregulation of tumor progression locus 2 (TPL-2), an upstream activator of extracellular signal related kinases (ERKs) in AAMs but not in CAMs, both at the transcript as well as the protein level. Pharmacologic inhibition of TPL-2 significantly diminished IL-10 production only in BCG-infected AAMs. Finally, we validated our findings in an in vivo C57Bl/6 model of filarial infection, where an exaggerated Th2 induced lung-specific alternative activation led to TPL-2 and IL-10 upregulation on subsequent TB infection. These data show that in response to mycobacterial infection, IL-4 generated AAMs in chronic filarial infections have impaired immune responses to TB infection by increasing IL-10 production in a TPL-2 mediated manner. Experimental rationale (microarray): To understand the effect of a pre-existing filiarial infection on the immune response of mice to Mycobacterium tuberculosis
2017-06-17 | GSE100105 | GEO
Project description:Wilson and King were among the first to recognize that the extent of phenotypic change between humans and great apes was dissonant with the rate of molecular change. Proteins are virtually identical; cytogenetically there are few rearrangements that distinguish ape-human chromosomes; rates of single-basepair change and retroposon activity have slowed particularly within hominid lineages when compared to rodents or monkeys. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orangutan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of basepairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single basepair mutations, there has been a genomic burst of duplication activity at this period during human evolution. A total of 8 humans, 8 chimpanzees and 8 orangutans were hybridized against the reference (NA15510, Clint and Susie, respectively).
2010-05-22 | E-GEOD-13885 | biostudies-arrayexpress
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Project description:Alternatively activated macrophages (AAMs) contribute to the resolution of inflammation and tissue repair. However, molecular pathways that govern their differentiation upon tissue damage have remained incompletely understood. Here, we show that the transcription factor GATA3 specifically controls the IL-4-independent differentiation of pro-resolving and reparative AAMs in response to injury and the necrotic cell-derived alarmin IL-33. In macrophages, IL-33 sequentially triggered an early expression of pro-inflammatory genes as well as a subsequent differentiation into AAMs. Global analysis of involved signaling events identified an IL-33-induced GATA-3 transcriptional module that specifically orchestrated AAM differentiation. IL-4-induced AAM differentiation, in contrast, was independent of GATA-3. Conditional deletion of GATA-3 in mononuclear phagocytes accordingly abrogated IL-33-induced differentiation of AAMs in vitro and diminished macrophage-mediated tissue repair in vivo. Our data thus identify an IL-33-GATA3 signaling axis that controls plasticity of macrophages in response to injury and fosters resolution of inflammation.
2021-10-06 | GSE151654 | GEO
Project description:Alternatively activated macrophages (AAMs) contribute to the resolution of inflammation and tissue repair. However, molecular pathways that govern their differentiation upon tissue damage have remained incompletely understood. Here, we show that the transcription factor GATA3 specifically controls the IL-4-independent differentiation of pro-resolving and reparative AAMs in response to injury and the necrotic cell-derived alarmin IL-33. In macrophages, IL-33 sequentially triggered an early expression of pro-inflammatory genes as well as a subsequent differentiation into AAMs. Global analysis of involved signaling events identified an IL-33-induced GATA-3 transcriptional module that specifically orchestrated AAM differentiation. IL-4-induced AAM differentiation, in contrast, was independent of GATA-3. Conditional deletion of GATA-3 in mononuclear phagocytes accordingly abrogated IL-33-induced differentiation of AAMs in vitro and diminished macrophage-mediated tissue repair in vivo. Our data thus identify an IL-33-GATA3 signaling axis that controls plasticity of macrophages in response to injury and fosters resolution of inflammation.
2021-10-06 | GSE151653 | GEO
Project description:Wilson and King were among the first to recognize that the extent of phenotypic change between humans and great apes was dissonant with the rate of molecular change. Proteins are virtually identical; cytogenetically there are few rearrangements that distinguish ape-human chromosomes; rates of single-basepair change and retroposon activity have slowed particularly within hominid lineages when compared to rodents or monkeys. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orangutan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of basepairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single basepair mutations, there has been a genomic burst of duplication activity at this period during human evolution. A total of 3 chimpanzees, 2 bonobos, 3 gorillas, 1 orangutan and 1 macaque were hybridized against human (NA15510). Other hybridizations (other humans, and non-humans) were also used as a replicate.
2010-05-22 | E-GEOD-13884 | biostudies-arrayexpress
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2019-11-12 | PXD013838 | Pride
Project description:Wilson and King were among the first to recognize that the extent of phenotypic change between humans and great apes was dissonant with the rate of molecular change. Proteins are virtually identical; cytogenetically there are few rearrangements that distinguish ape-human chromosomes; rates of single-basepair change and retroposon activity have slowed particularly within hominid lineages when compared to rodents or monkeys. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orangutan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of basepairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single basepair mutations, there has been a genomic burst of duplication activity at this period during human evolution.
2009-03-06 | GSE13885 | GEO
Project description:Wilson and King were among the first to recognize that the extent of phenotypic change between humans and great apes was dissonant with the rate of molecular change. Proteins are virtually identical; cytogenetically there are few rearrangements that distinguish ape-human chromosomes; rates of single-basepair change and retroposon activity have slowed particularly within hominid lineages when compared to rodents or monkeys. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orangutan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of basepairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single basepair mutations, there has been a genomic burst of duplication activity at this period during human evolution.
2009-03-06 | GSE13884 | GEO