Therefore, we studied embryos in which heart development was arrested after 2 days of incubation, and found that yolk sac growth and blood peripheral accumulation still occurred. We hypothesized that the driving force for the primitive blood flow is a growth-induced gradient of tissue pressure in the yolk sac mesoderm.

We report that blood accumulation starts before heart-induced blood circulation. Here we study the peripheral accumulation of blood in the chicken embryonic yolk sac, which precedes sinus vein formation. Only little attention has been paid to the impact of mechanical stress caused by tissue growth on early blood distribution. Understanding how molecular and physical cues orchestrate vascular morphogenesis is a challenge for developmental biology. Our findings place Eomes at the top of the transcriptional hierarchy regulating early blood formation and suggest that haemogenic competence is endowed earlier during embryonic development than was previously appreciated.

Single-cell RNA sequencing suggests that Eomes loss of function profoundly blocks the formation of blood progenitors but not specification of Flk-1⁺ haematoendothelial progenitors. Eomes regulates the accessibility of enhancers that the transcription factor stem cell leukaemia (SCL) normally utilizes to specify primitive erythrocytes and is essential for the normal development of Runx1⁺ haemogenic endothelium. Here we demonstrate using an embryonic stem cell model that transient expression of the T-box transcription factor Eomesodermin (Eomes) governs haemogenic competency of ExM. How a specific subset of ExM becomes committed to a haematopoietic fate remains unclear. Our results suggest that the endothelial origin of primitive blood cells is direct and does not include the intermediate step of primitive hematopoietic progenitors.Įxtra-embryonic mesoderm (ExM)-composed of the earliest cells that traverse the primitive streak-gives rise to the endothelium as well as haematopoietic progenitors in the developing yolk sac. We also provide evidence that MYB is essential for neutrophil and T cell development and the upregulation of innate immunity genes during hematopoietic differentiation. Here we show that the disruption of the MYB gene leads to severe defects in the development and proliferation of primitive hematopoietic progenitors while the emergence of primitive blood cells is not affected. The differentiation of the reporter cell lines demonstrated that MYB is specifically expressed throughout emerging hematopoietic cell populations. To recapitulate the early developmental events more adequately, the mutant and wild type human embryonic stem cell lines were differentiated in defined culture conditions without the addition of hematopoietic cytokines. To delineate definitive versus primitive hematopoiesis during differentiation of human embryonic stem cells, we have introduced reporters into the MYB locus and inactivated the gene by bi-allelic targeting. MYB is a key regulator of definitive hematopoiesis and it is dispensable for the development of primitive hematopoietic cells in vertebrates.

Blood island