Project description:Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.
Project description:The understanding of human early embryo developoment is very import for us to resovle the mysteries of how human organs especially the brain works and how human disease come up.Therefor, we carried out single cell RNA-seq and spatial transcriptional RNA-seq of human early embryo and analysed gene expression dynamics during the embryo development.We found some import genes and pathways that may control the ongoing of development.These findings help us make a step in understanding how we human being grow from a simple embryo to a complex one.
Project description:These data were used in the spatial transcriptomics analysis of the article titled \\"Single-Cell and Spatial Transcriptomics Analysis of Human Adrenal Aging\\".
Project description:Spatial localization is a key determinant of cellular fate and behavior, but spatial RNA assays traditionally rely on staining for a limited number of RNA species. In contrast, single-cell RNA-seq allows for deep profiling of cellular gene expression, but established methods separate cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos, inferring a transcriptome-wide map of spatial patterning. We confirmed Seurat’s accuracy using several experimental approaches, and used it to identify a set of archetypal expression patterns and spatial markers. Additionally, Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems. We generated single-cell RNA-seq profiles from dissociated cells from developing zebrafish embryos (late blastula stage - 50% epiboly)
Project description:Human cerebellar development is precisely orchestrated by molecular regulatory networks. Here, we combined single-cell transcriptomics, spatial transcriptomics and chromatin accessibility states to systematically depict an integrative temporal-spatial landscape of human fetal cerebellar development. The multiomic data reveal molecular networks, providing an informative regulatory map to show how and when cell fates are determined. Spatial transcriptomics illustrated the distinct molecular signatures of the progenitors, Purkinje cells and granule cells located in different regions of the developing cerebellar cortex. We identified RORB as a new marker of developing human Purkinje cells, which was not expressed in mice. In addition, the RL progenitors highly expressed the human-specific gene ARHGAP11B , and ARHGAP11B expression led to cerebellar cortex expansion and folding in mice. We finally mapped the genes and single-nucleotide polymorphisms (SNPs) of diseases related to cerebellar dysfunction onto cell types, indicating the cellular basis and possible pathogenesis mechanisms of neuropsychiatric disorders.
Project description:We performed spatial transcriptomic experiments using the 10x Visium assay, generating high-quality transcriptomic profiles for samples from PCW5 to PCW8