Spatiotemporal transcriptome of the human brain
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PROVIDER: PRJNA76029 | ENA |
REPOSITORIES: ENA
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Project description:<p>Comprehensive knowledge about the spatiotemporal dynamics of the brain transcriptome is essential for a better understanding of neurodevelopment, sexual dimorphism, and evolution, as well as our increased susceptibility to certain brain disorders. We generated and analyzed genome-wide exon-level transcriptome data from 16 brain regions of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genome-wide genotyping of 2.5 million SNPs and assessed genome normality for all donors. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of human neurodevelopment.</p>
| phs000406.v1.p1 | EGA
Project description:The development of the human brain is a complex and precisely regulated process that unfolds over a protracted period of time. Human-specific features of this process, especially the ways in which highly complex neural circuits of the cerebral cortex form, are likely to be important factors in the evolution of human specializations. However, in addition to giving us remarkable cognitive and motor abilities, the formation of intricate neural circuits may have also increased our susceptibility to psychiatric and neurodegenerative disorders. Furthermore, substantial evidence suggests that the symptoms and progression of many brain disorders are dramatically influenced by genetic and developmental processes that define regional cell phenotypes and connectivity. Sex differences also play an important role in brain development and function and are a risk factor for several brain disorders, such as autism spectrum disorders (ASD) and depression. Thus understanding the spatiotemporal dynamics and functional organization of the brain transcriptome is essential to teasing out the keys to human neurodevelopment, sexual dimorphism, and evolution as well as our increased susceptibility to certain brain disorders. Most transcriptome studies of the developing brain have been restricted to rodents, and those performed in humans and nonhuman primates have included relatively small sample sizes and predominantly focused on few regions or developmental time points. Because many prominent features of human brain development significantly diverge from those of well-characterized model organisms, the translation of knowledge across species is difficult, and it is likely that many underlying genetic processes have gone undetected. In this study, we have taken a genome-wide approach to analyze the human transcriptome at single-exon resolution with ~1.4 million exon-level probe sets in 16 brain regions from donors representing both sexes and multiple ethnicities, across pre and postnatal development, including adolescence, and adulthood. We also generated genome-wide genotype data for 2.5 million single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for each specimen. Our analyses of the data revealed several features of the human brain transcriptome: spatiotemporal expression dynamics of individual and functionally related groups of genes, differential exon usage, sex-specific expression patterns and exon usage, and organization of the transcriptome into functional modules. We also profiled developmental trajectories of genes important for neurobiological themes and genes associated with ASD and schizophrenia. Finally, we present associations between specific SNPs and gene expression levels in different brain regions across development. The dataset presented here provides research opportunities and a wealth of information not previously available to the scientific community. Here we report the generation and analysis of genome-wide exon-level transcriptome data from 16 brain regions comprising the cerebellar cortex, mediodorsal nucleus of the thalamus, striatum, amygdala, hippocampus, and 11 areas of the neocortex. The dataset was generated from 1,340 samples collected from both hemispheres of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genome-wide genotyping of 2.5 million single nucleotide polymorphisms (SNPs) and assessed copy number variations for all donors. We found that approximately 86% of protein-coding genes are expressed above background, and over 90% of these are differentially regulated at the whole transcript or exon level across regions and/or time. The majority of these spatiotemporal differences occur before birth, followed by a progressive increase in the similarity among regional transcriptome during the postnatal lifespan. Distinctive transcriptional patterns were also identified among neocortical areas, including an alternative isoform of ANKRD32 that is transiently upregulated in the late midfetal frontal cortex of human but not mouse. Developmentally and regionally regulated differences in gene expression and exon usage were also identified between males and females, including IGF2, an imprinted gene implicated in brain growth and cognitive function, and NLGN4X, a candidate gene for autism spectrum disorders. We found that the developing transcriptome is organized into functionally distinct large-scale networks of co-regulated transcripts. We also observed marked differences in expression trajectories of genes associated with specific neurodevelopmental processes, neural cell types, neurotransmitter systems, autism spectrum disorders, and schizophrenia. Association analysis of the SNP genotypes and transcriptome revealed potential polymorphic regulators of gene expression in different regions across development. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of brain development and evolution. This submission represents the transcriptome component of the study. Submitter did not submit SNP and CNV data due to privacy issue of patients.
2011-10-26 | E-GEOD-25219 | biostudies-arrayexpress
Project description:The development of the human brain is a complex and precisely regulated process that unfolds over a protracted period of time. Human-specific features of this process, especially the ways in which highly complex neural circuits of the cerebral cortex form, are likely to be important factors in the evolution of human specializations. However, in addition to giving us remarkable cognitive and motor abilities, the formation of intricate neural circuits may have also increased our susceptibility to psychiatric and neurodegenerative disorders. Furthermore, substantial evidence suggests that the symptoms and progression of many brain disorders are dramatically influenced by genetic and developmental processes that define regional cell phenotypes and connectivity. Sex differences also play an important role in brain development and function and are a risk factor for several brain disorders, such as autism spectrum disorders (ASD) and depression. Thus understanding the spatiotemporal dynamics and functional organization of the brain transcriptome is essential to teasing out the keys to human neurodevelopment, sexual dimorphism, and evolution as well as our increased susceptibility to certain brain disorders. Most transcriptome studies of the developing brain have been restricted to rodents, and those performed in humans and nonhuman primates have included relatively small sample sizes and predominantly focused on few regions or developmental time points. Because many prominent features of human brain development significantly diverge from those of well-characterized model organisms, the translation of knowledge across species is difficult, and it is likely that many underlying genetic processes have gone undetected. In this study, we have taken a genome-wide approach to analyze the human transcriptome at single-exon resolution with ~1.4 million exon-level probe sets in 16 brain regions from donors representing both sexes and multiple ethnicities, across pre and postnatal development, including adolescence, and adulthood. We also generated genome-wide genotype data for 2.5 million single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for each specimen. Our analyses of the data revealed several features of the human brain transcriptome: spatiotemporal expression dynamics of individual and functionally related groups of genes, differential exon usage, sex-specific expression patterns and exon usage, and organization of the transcriptome into functional modules. We also profiled developmental trajectories of genes important for neurobiological themes and genes associated with ASD and schizophrenia. Finally, we present associations between specific SNPs and gene expression levels in different brain regions across development. The dataset presented here provides research opportunities and a wealth of information not previously available to the scientific community.
2011-10-27 | GSE25219 | GEO
Project description:During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using a dual reporter cell line to isolate neural progenitors and neurons from the telencephalic brain organoid tissue and performed cell type and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed temporal modules of gene expression during human corticogenesis, both at RNA and protein level. Our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for fidelity of cortical development.
2022-10-25 | PXD037106 | Pride
Project description:Spatiotemporal Analysis of the Human Cerebellum
| PRJNA575583 | ENA
Project description:Spatiotemporal Analysis of the Human Cerebellum
| PRJNA575584 | ENA
Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
2022-08-12 | PXD033420 | Pride
Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
2022-08-12 | PXD034449 | Pride
Project description:Spatiotemporal transcriptome of the mouse dentate gyrus
| PRJNA439378 | ENA
Project description:Profiling the piRNA transcriptome of the human brain
| PRJEB71709 | ENA