Project description:We produced an extensive transcript catalog for LCLs of 5 primate species by leveraging isoform sequencing and short-read RNA-seq. The curated transcriptomes were used to assist mass spectrometry protein identifications.
Project description:Key to the human brain’s unique capacities are a myriad of neural cell types, specialized molecular expression signatures, and complex patterns of neuronal connectivity. Neurons in the human brain communicate via well over a quadrillion synapses. Their specific contribution might be key to the dynamic activity patterns that underlie primate-specific cognitive function. Recently, functional differences were described in transmission capabilities of human and rat synapses. To test whether unique expression signatures of synaptic proteins are at the basis of this, we performed a quantitative analysis of the hippocampal synaptic proteome of four mammalian species, two primates, human and marmoset, and two rodents, rat and mouse. Abundance differences down to 1.15-fold at an FDR-corrected p-value of 0.005 were reliably detected using SWATH mass spectrometry. The high measurement accuracy of SWATH allowed the detection of a large group of differentially expressed proteins between individual species and rodent versus primate. Differentially expressed proteins between rodent and primate were found highly enriched for plasticity-related proteins.
Project description:Embryonic development is largely conserved among mammals. However, certain genes show divergent functions. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we uncover that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 results in non-human primate embryos which do not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos display a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirm a similar role of ISL1 in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.
2021-06-30 | GSE148683 | GEO
Project description:Evolution of primate piRNA clusters
Project description:Our knowledge of genomic imprinting in primates is lagging behand that of mice largely due to the difficulties of allelic analyses in outbred animals. To understand imprinting dynamics in primates, we profiled transcriptomes, DNA methylomes and H3K27me3 in uniparental monkey embryos. We further developed single-nucleotide polymorphisms (SNP)-free methods, TARSII and CARSII, to identify germline differentially methylated regions (DMRs) in somatic tissues. Our comprehensive analyses showed that allelic DNA methylation, but not H3K27me3, is a major mark that correlates with paternal-biasedly expressed genes (PEGs) in uniparental monkey embryos. Interestingly, primate germline DMRs are different from PEG-associated DMRs in early embryos and are enriched in placenta. Strikingly, most placenta-specific germline DMRs are lost in placenta of cloned monkey. Collectively, our study establishes SNP-free germline DMR identification methods, defines developmental imprinting dynamics in primates and demonstrates imprinting defects in cloned monkey placenta, which provides important clues for improving primate cloning.
Project description:Molecular characterization of the individual neuron types existing in the primate dorsal root ganglion and the relation to model organisms used for studying somatosensation and pain is critical for understanding the cellular origin of chronic pain and for translational aspects of biomedical research. However, molecular insights into the primate dorsal root ganglion are missing and a systematic comparison of strategies for somatosensation between the mouse and primates is lacking. Here we classify non-human primate sensory neurons based on their transcriptome and identify neuronal types with heritability to chronic pain. We identify nine neuronal types and use machine learning to expose an overall cross-species conserved strategy and shared taxonomy for nociception, although with differences at individual gene level, highlighting the importance of incorporating primate knowledge for the successful translation of discoveries in rodent model organisms. Genomic loci implicated in chronic pain were mapped onto specific primate sensory neuron types to identify the cellular origin of chronic pain. The common-variant genome-wide association results for chronic pain point to the same cells at the same pain sites and concentrate on two different neuronal types between pain disorders, suggesting that causative cell types and molecular mechanisms are different between different pain conditions.