Project description:<p>Elucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. In this study, we applied single nucleus RNA sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhibitory neuronal types, many of which are relatively sparse. Additionally, we found that excitatory types are less layer-restricted than expected based prior knowledge from cell morphologies and from mouse studies. Comparison to a similar mouse cortex single cell RNA-sequencing dataset revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous cell types in human and mouse, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain.</p> <p>This study conducted by the Allen Institute for Brain Science was supported by the Allen Institute for Brain Science and by US National Institutes of Health grant U01 MH114812-02 to E.S.L. Collaborators request that publications resulting from these data cite their original publication: Hodge RD, Bakken TE, et al. Conserved cell types with divergent features between human and mouse cortex. bioRxiv. 2018 doi: <a href="https://www.biorxiv.org/content/10.1101/384826v1" target="_blank">10.1101/384826</a>.</p>
Project description:Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.
Project description:To explore how brains change upon species evolution, we generated the first whole central brain comparative single-cell transcriptomic atlases of three closely-related but ecologically-distinct drosophilids: D. melanogaster, D. simulans and D. sechellia. D. melanogaster and D. simulans are cosmopolitan generalists, while the island endemic D. sechellia exhibits extreme niche specialism on the ripe noni fruit of the Morinda citrifolia shrub. The global cellular composition of central brains is well-conserved in the three Drosophila species, but we predicted a few cell types (perineurial glia, sNPF and Dh44 neurons) with divergent frequencies. Gene expression analysis revealed that distinct cell types within the central brain evolve at different rates and patterns; notably, several glial cell types exhibit the greatest divergence between species. Compared to D. melanogaster, the cellular composition and gene expression patterns of the central brain in D. sechellia displays greater deviation than those of D. simulans, indicating that the distinctive ecological specialization of D. sechellia is reflected in the structure and function of its brain. Gene expression changes in D. sechellia encompass metabolic and ecdysone signaling genes, indicative of adaptations to its novel ecological demands. Additional single-cell transcriptomic analysis on D. sechellia revealed genes and cell types responsive to noni juice supplementation, showing glial cells as key sites for both physiological and genetic adaptation to novel conditions. Our comparative transcriptomic atlases of drosophilid brains will provide an entry point to more broadly study the evolvability of nervous systems across and beyond the Drosophila genus.
Project description:Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and the conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our understanding of human and mouse kidney development, we profiled chromatin organization (ATAC-seq) and gene expression (RNA-seq) in developing human and mouse kidneys. Data were analyzed at a species level and then integrated into a common, cross-species multimodal data set. Comparative analysis of cell types and developmental trajectories identified conserved and divergent features of chromatin organization and linked gene activity, revealing species- and cell-type specific regulatory programs. Identification of human-specific enhancer regions linked through GWAS studies to kidney disease highlights the potential of developmental modeling to provide clinical insight.
Project description:Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and the conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our understanding of human and mouse kidney development, we profiled chromatin organization (ATAC-seq) and gene expression (RNA-seq) in developing human and mouse kidneys. Data were analyzed at a species level and then integrated into a common, cross-species multimodal data set. Comparative analysis of cell types and developmental trajectories identified conserved and divergent features of chromatin organization and linked gene activity, revealing species- and cell-type specific regulatory programs. Identification of human-specific enhancer regions linked through GWAS studies to kidney disease highlights the potential of developmental modeling to provide clinical insight.
Project description:Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and the conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our understanding of human and mouse kidney development, we profiled chromatin organization (ATAC-seq) and gene expression (RNA-seq) in developing human and mouse kidneys. Data were analyzed at a species level and then integrated into a common, cross-species multimodal data set. Comparative analysis of cell types and developmental trajectories identified conserved and divergent features of chromatin organization and linked gene activity, revealing species- and cell-type specific regulatory programs. Identification of human-specific enhancer regions linked through GWAS studies to kidney disease highlights the potential of developmental modeling to provide clinical insight.
Project description:Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and the conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our understanding of human and mouse kidney development, we profiled chromatin organization (ATAC-seq) and gene expression (RNA-seq) in developing human and mouse kidneys. Data were analyzed at a species level and then integrated into a common, cross-species multimodal data set. Comparative analysis of cell types and developmental trajectories identified conserved and divergent features of chromatin organization and linked gene activity, revealing species- and cell-type specific regulatory programs. Identification of human-specific enhancer regions linked through GWAS studies to kidney disease highlights the potential of developmental modeling to provide clinical insight.
Project description:Genome-wide Analysis Reveals Conserved and Divergent Features of Notch1/RBPJ Binding in Human and Murine T Lymphoblastic Leukemia Cells