Similar Datasets
Project description:RNA interference (RNAi) for spinocerebellar ataxia type 1 can prevent and reverse behavioral deficits and neuropathological readouts in mouse models, with safety and benefit lasting over many months. The RNAi trigger, expressed from adeno-associated virus vectors (AAV.miS1), also corrected misregulated microRNAs (miRNA) such as miR150. Subsequently, we showed that the delivery method was scalable, and that AAV.miS1 was safe in short-term pilot nonhuman primate (NHP) studies. To advance the technology to patients, investigational new drug (IND)-enabling studies in NHPs were initiated. After AAV.miS1 delivery to deep cerebellar nuclei, we unexpectedly observed cerebellar toxicity. Both small-RNA-seq and studies using AAVs devoid of miRNAs showed that this was not a result of saturation of the endogenous miRNA processing machinery. RNA-seq together with sequencing of the AAV product showed that, despite limited amounts of cross-packaged material, there was substantial inverted terminal repeat (ITR) promoter activity that correlated with neuropathologies. ITR promoter activity was reduced by altering the miS1 expression context. The surprising contrast between our rodent and NHP findings highlight the need for extended safety studies in multiple species when assessing new therapeutics for human application.
| S-EPMC8605996 | biostudies-literature
Project description:Toxicity after AAV delivery of RNAi expression constructs into nunhuman primate brain
| PRJNA757392 | ENA
Project description:We used single-nuclei sequencign to determine the effect of chorioamnionitis to the developing cerebellum using a rhesus macaque model of chorioamnionitis induced by intra-amniotic LPS.
2024-01-17 | GSE205001 | GEO
Project description:While genome sequencing has identified numerous non-coding alterations between primate species, which of these are regulatory and potentially relevant to the evolution of the human brain is unclear. Here, we annotate cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee genome using ChIP-sequencing in different anatomical parts of the adult brain. We find high similarity in the genomic positioning of CREs between rhesus macaque and humans, suggesting that the majority of these elements were already present in a common ancestor 25 million years ago. Most of the observed regulatory changes between humans and rhesus macaque occurred prior to the ancestral separation of humans and chimpanzee, leaving a modest set of regulatory elements with predicted human-specificity. Our data refine previous predictions and hypotheses on the consequences of genomic changes between primate species, and allow the identification of regulatory alterations relevant to the evolution of the brain. ChIP-Sequencing for H3K27ac on 8 distinct brain regions from human (three biological replicates per brain region), chimpanzee (two biological replicates per brain region) and rhesus macaque (three biological replicates per brain region).
2016-01-13 | E-GEOD-67978 | biostudies-arrayexpress
Project description:We report single-nucleus transcriptomes from brain regions in 5 species: mice: Frontal Cortex, V1, Hippocampus, Striatum; common marmoset: 7 neocortical regions, Hippocampus, Striatum (Nucleus Accumbens, Caudate, Putamen); rhesus macaque: Prefrontal Cortex, V1; human: Prefrontal Cortex, V1, Striatum (Caudate); ferret: Prefrontal Cortex, V1, Striatum
2020-06-04 | GSE151761 | GEO
Project description:While genome sequencing has identified numerous non-coding alterations between primate species, which of these are regulatory and potentially relevant to the evolution of the human brain is unclear. Here, we annotate cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee genome using ChIP-sequencing in different anatomical parts of the adult brain. We find high similarity in the genomic positioning of CREs between rhesus macaque and humans, suggesting that the majority of these elements were already present in a common ancestor 25 million years ago. Most of the observed regulatory changes between humans and rhesus macaque occurred prior to the ancestral separation of humans and chimpanzee, leaving a modest set of regulatory elements with predicted human-specificity. Our data refine previous predictions and hypotheses on the consequences of genomic changes between primate species, and allow the identification of regulatory alterations relevant to the evolution of the brain.
2016-01-13 | GSE67978 | GEO
Project description:This experiment contains the subset of data corresponding to rhesus macaque RNA-Seq data from experiment E-GEOD-30352 (http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-30352/), which goal is to understand the dynamics of mammalian transcriptome evolution. To study mammalian transcriptome evolution at high resolution, we generated RNA-Seq data (∼3.2 billion Illumina Genome Analyser IIx reads of 76 base pairs) for the polyadenylated RNA fraction of brain (cerebral cortex or whole brain without cerebellum), cerebellum, heart, kidney, liver and testis (usually from one male and one female per somatic tissue and two males for testis) from nine mammalian species: placental mammals (great apes, including humans; rhesus macaque; mouse), marsupials (gray short-tailed opossum) and monotremes (platypus). Corresponding data (∼0.3 billion reads) were generated for a bird (red jungle fowl, a non-domesticated chicken) and used as an evolutionary outgroup.
2011-10-12 | E-MTAB-3717 | biostudies-arrayexpress
Project description:We have quantified gene expression in five tissues (brain, heart, kidney, liver and testis) from humans, chimpanzees and rhesus macaques using the Illumina NlaIII Digital Gene Expression (DGE) protocol. This dataset extends a previous microarray study by Khaitovich et al. (Khaitovich et al. 2005) with the rhesus macaque outgroup and complements other previously generated tissue transcriptome profiles from primates (Enard et al. 2002; Khaitovich et al. 2006; Somel et al. 2009; Babbitt et al. 2010; Blekhman et al. 2010; Wetterbom et al. 2010). contributor: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany
2013-10-01 | GSE50782 | GEO
Project description:Model animals are employed in experiments as substitutes for human tissues and fluids, particularly when accessing particular human samples (such as cerebrospinal fluid, brain, ocular tissues, etc.) poses significant challenges or is ethically constrained. Nonhuman primates are frequently regarded as superior animal models for investigating human ophthalmological diseases. However, despite this recognition, the metabolomic composition of ocular tissues in non-human primates remains predominantly unexplored. In this work, we present a dataset on metabolite concentrations in serum and ocular tissues, including aqueous humor (AH), vitreous humor (VH), and lens, in two Macaque species: crab-eating macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta). A total of 99 compounds were quantified in 45 samples, shedding light on the previously unknown metabolomic profiles of primate eye tissues.
2023-11-16 | MTBLS8943 | MetaboLights
Project description:Induced pluripotent stem cells (iPSCs) hold promise for generating personalized xenogenic organs via development of cross-species chimeric animals. However, whether human and other primate iPSCs are capable of establishing cross-species chimeras remains unknown. Recognizing the ethical concerns of cross-species chimerism using human iPSCs, we explored the capacity for cross-species chimerism between distinct, non-human primates. Injection of either pig-tailed macaque iPSCs or chimpanzee iPSCs into the rhesus macaque blastocyst embryos demonstrated that these cells survive, proliferate, and integrate near the rhesus inner cell mass (ICM). Ectopic expression of BCL2 in pig-tailed and chimpanzee iPSCs greatly improved the success rate of establishing cross-species blastocyst chimerism. This study represents the first successful cross-species blastocyst chimerism between distinct, non-human primate species, and highlights critical factors that may be necessary to unlock the broad potential of primate iPSCs to form cross-species chimeras, with diverse applications for basic research and translational medicine.
2020-09-30 | GSE155443 | GEO