The study was led by @chao_yiming now on job market.

Blood originates in hypoblasts during embryonic development

www.biorxiv.org/cgi/content/...

- The first blood comes from the hypoblast that contributes to hemoglobin+ phagocyte-like cells;

- CDX2 marks hypoblast blood that sustains oxygen supply in embryos before heart formation;

- Erythro-core regulatory network endows erythropoiesis to human hypoblasts and phagocytes.

Now we employ CRISPRa and are discovering a core regulatory network to endow erythropoiesis to hypoblast as well as phagocytes. 8/

Indeed, the red cell precursor from hypoblast is mesenchymal and EMT+. What’s more, they are molecularly and functionally similar to phagocytes. What does it mean? Phagocytes are one of the oldest immune cells in evo-devo. What if hypoblast repurposed a phagocyte to give a new role? Carry oxygen? 7/

But the remaining question is, why do we need to make red blood cells so early?
We are actually a macrophage lab, and got inspired at GRC Phagocytes this year.
The heart beats 1 week after blood appears. Blood should do its job without circulation. Should the early blood be snaky and locomotive…? 6

We used two independent human embryo models and LARRY molecular barcoding to identify hypoblast transition to erythroblasts. CDX2 marks such a transition, and its KO led embryo model suffers hypoxia. 5/

Hypoblast was believed to be a dead end of development, only contributing to the yolk sac structure, or AVE. But primate embryos suggest hypoblast may contribute to extraembryonic mesenchymal cells, that we saw in our human embryo models too. 4/

We wondered if some blood might begin before gastrulation. These are epiblast, trophoblast, and hypoblast. Epiblast undergoes gastrulation to follow the long track to make blood. Trophoblast is missing in some embryo models, but we still see such early blood. Then hypoblast…? 3/

We hematologists are taught that all blood starts from gastrulation. When we precisely followed these steps that mimic gastrulation, hematoendothelial mesoderm, and hematopoiesis, it took 2 weeks. But some red cell precursors appear much faster, like a few days… 2/