Spatiotemporal dissection of the developmental origins of the endothelial lineage during mouse gastrulation

In embryonic development, endothelial cells (EC) develop from hematoendothelial (HE) progenitors of mesodermal origin and form the early blood vessel network in a process known as vasculogenesis. HE progenitors that express key early markers such as Kdr have been identified in nascent embryonic structures like the yolk sac, allantois, heart and brain. However it is still unclear whether they are specified independently from local populations or, alternatively, diverge from a single source to colonize these tissues.

We have recently used single-cell transcriptomics to generate a time-resolved model of mouse gastrulation that describes gene dynamics along cellular trajectoriesof mouse gastrulation and predict lineage progression. Intriguingly, our analysis predicts that while most lineages diverge with time to transcriptionally distinct states, ECs are contributed from at least four distinct local sources that converge to a similar transcriptional state. Spatiotemporal analysis

To substantiated this cconvergent model, we are currently performing lineage tracing experiments, single-molecule FISH analysis and other approaches.differentiation underlying specification of embryonic ECs from distinct local progenitors. Likewise,

utemporal multi-omic measurements of DNA accessibility and RNA from the same cells identified putative cis-regulatory elements (CREs) of associated with the activation of KDR associated with distinctin discrete populations of HE progenitors contributing to the EC lineage, in agreement with a local, convergent model of EC specification. To study and validate their role in EC development, we analyzed the role of individual CREs in chimeric embryos. Collectively, our work establishes a comprehensive, time-resolved model of EC specification during gastrulation.