Project description:To comprehensively delineate the ontogeny of an organ system, we generated 112,217 single- cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio- temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.
Project description:To comprehensively delineate the ontogeny of an organ system, we generated 112,217 single- cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio- temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.
Project description:Current gene-expression databases for the haematopoietic system provide information on gene expression profiles present in bulk populations. Although informative, these studies lack the resolution that can be gained at a single-cell level. In particular, population-average data assumes homogeneity within the population and may as such obscure the ability to detect the heterogeneity of decision-making processes in individual cells. Here we report 1656 single cell transcriptomes analysed by single-cell RNA sequencing. Cells were FACS sorted on broad gates encompassing haematopoietic stem and progenitor populations (HSPCs), with index sorting data collected to permit retrospective identification of populations by surface marker expression. Our dataset thus represents the gene expression landscape of HSPCs at single-cell resolution, capturing the heterogeneity in and between cell populations. Pseudotime analysis visualized haematopoietic stem (HSC) to progenitor transitions, identified HSC as well as lineage-specific transcriptional programs, and also highlighted putative lineage branching points. To provide access to the wider scientific community, a user-friendly website was developed with intuitive search and display functionality. Single cell RNA sequencing of haematopoeitic stem and progenitor cells