Blood and cardiovascular development represent paradigms of embryonic organ formation, with increasingly specialised cells generated from early mesoderm. Here, we map the progression of mesoderm towards blood by single cell expression analysis of 3,934 cells, aiming to capture an entire embryo equivalent of cells with blood-forming potential at four sequential developmental stages. Using novel computational approaches, we reconstruct the developmental journey at single cell resolution, which reveals asynchrony of maturation and sequential waves of expression for major regulators. Considering transitions between individual cellular states, we synthesise executable transcriptional regulatory network models that recapitulate blood development. Using mouse embryos and embryonic stem cells, we validate model predictions by showing that Sox7 inhibits primitive erythropoiesis, and that Sox and Hox factors control early expression of Erg. We therefore demonstrate that single cell analysis of a developing organ coupled with novel computational approaches can reveal the transcriptional programs that control organogenesis. SOURCE: Evangelia Diamanti (ed347@cam.ac.uk) - Gottgens University of Cambridge

Pluto Bioinformatics

GSE61470: Decoding the Transcriptional Program for Blood Development from Single Cell Gene Expression Measurements