ABSTRACT: To isolation of high-yield and viable brain cells including neurons and neural progenitors from adult primate brains, we have developed a reproducible whole-cell dissociation procedure for isolation of primary brain cells from adult and aged primates, with high-yield progenitor, immature and mature neural cells. We verified the viability of isolated cells and identified the main cell type with canonical markers. Furthermore, isolated primate neural progenitors by this our protocol is viable enough for culturing in vitro. This dataset is a detailed single cell RNA-sequencing results for two primate brain regions: primary visual cortex and prefrontal cortex.
Project description:With improved whole-cell isolation protocols, we performed single-cell RNA sequencing (scRNA-seq) and profiled the transcriptomes from adult non-human primate brain. We identified discriminative cell populations with canonical and novel markers. Cross-species projection demonstrated the evolutionary conservation among mouse, monkey, and human. This dataset serves as a detailed transcriptomic atlas for understanding the adult primate central nervous system.
Project description:The human brain has changed dramatically from other primate species, but the genetic and developmental mechanisms behind the differences remains unclear. Here we used single cell RNA sequencing based on 10X technology to explore temporal transcriptomic dynamics and cellular heterogeneity in cerebral organoids derived from human and non-human primates chimpanzee and rhesus macaque stem cells. Using cerebral organoids as a proxy of early brain development, we detect a delayed pace of human brain development relative to the other two primate species. Additional human-specific gene expression patterns resolved to different cell states through progenitors to neurons are also found. Our data provide a transcriptomic cell atlas of primate early brain development, and illustrate features that are unique to humans.
Project description:Explore DNA methylation in traumatic brain injury model of epilepsy and its relationship to gene expression. Examination of methylation changes in stimulated rats compared to sham operated animals in traumatic brain injury model of epilepsy.
Project description:Explore DNA methylation in traumatic brain injury model of epilepsy and its relationship to gene expression. Examination of expression changes in stimulated rats compared to sham operated animals in traumatic brain injury model of epilepsy.
Project description:In this project we studied the effect of Langat infection (LGTV strain TP21) on the brains of mice, both wild-type and Ifnar-/-. Nuclei of the brain were isolated and subjected to 10x 3' scRNAseq.
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.
Project description:The largest germinal niche of the adult mammal brain locates at the ventricular zone (VZ), which is made up of adult neural stem cells (NSCs) and multiciliated ependymal cells (EPCs). Both NSCs and EPCs derive from radial glia (RG), whereas the transcriptomic dynamic changes of the cell fate continuum remain elusive. Here, we used single cell RNA-seq of CD133 positive RGCs from the VZ of new born mice to uncover the developmental trajectories of RGCs to NSCs and EPCs.
Project description:Time dependent-profiles in the gene expression level following lateral moderate fluid percussion injury in the rat brain We used microarray to elucidate relationship between the alteration of gene expression levels and the progression of brain damages following traumatic brain injury. To examine the levels of gene expression in the early phase of traumatic brain injury, we analyzed the gene expression at 3, 6, 12, and 48 h after trauma using the lateral moderate fluid percussion TBI model. The ratios of the gene expression level were compared between chips corresponding to the 3, 6 and 12 h fluid percussion groups and the sham group chips. On the other hand, the rations of gene expression level after 48 h FPI were compared with 48 h sham chip, because the gene expression levels of 48 h sham chip were distinct from sham group chips (3, 6 and 12 h) in the cluster and principal components analyses.
Project description:Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which of these changes are biologically relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains disproportionally affect oligodendrocyte function after postnatal development and are preferentially affected in the brains of autism spectrum disorder patients. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.
Project description:The aim of this work is to describe the transcriptomic changes underlying the complex mechanisms of the host response to pneumococcal meningitis in a temporal and spatial context. For this purpose we evaluated the gene expression profile of the two brain structures predominantly affected by brain damage i.e. the cortex and the hippocampus at four different stages of the disease (24-, 72-, 240- and 624 hours post infection) using an infant rat model. <br><br>The first two timepoints represent the acute and late disease phase of bacterial meningitis (BM) and 10 and 26days the recovery phase. At each timepoint 6 infected and 6 sham infected animals were sacrificed. Control and infected animals were age matched to avoid differences in the gene expression patterns due to developmental processes in the infant rat brain.