GSE204896
A trio of bipotent precursors seeds the mesenchymal, haematopoietic, and endothelial lineages of the yolk sac
During embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro has revealed a mesenchymal differentiation potential, a feature more compatible with an earlier mesodermal precursor. To date, no evidence for an in vivo haemangioblast has been discovered. Using single cell RNA-Sequencing and in vivo cellular barcoding, we have unraveled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. We show that the mesodermal derivatives of the yolk sac are produced by three distinct bipotential precursors: the haemangioblast, mesenchymoangioblast, and a novel cell type: the haematomesoblast. Between E6.5 and E7.5, this trio of precursors seeds haematopoietic, endothelial, and mesenchymal trajectories. Overall design: This single cell RNAseq dataset was aimed at characterising non-blood, non endothelial components of the yolk sac. A pool of 33 C57BL/6 yolk sacs was enzymatically dissociated to generate a single cell suspension. 6 populations were sorted (primitive erythrocyte (EryP: TER119+ CD45-), haematopoietic progenitor/colony forming cell (HPC: TER119- CD41low CD45+), Megakaryocyte (Mk: TER119- CD41high CD45-), macrophage (Mac: TER119- CD41- CD45+), endothelium (Endo: TER119- CD41- CD45- PECAM+ PDGFRA-), mesenchyme (Mes: TER119- CD41- CD45- PECAM-)).  Each population was labelled with a unique MultiSeq hashtag to identify population of origin. Sorted cells were combined and loaded on the 10X Chromium.