Identification and characterization of human hematopoietic mesoderm.

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases. It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage. In this study, we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos, enabling us to identify and define the molecular features of human hematopoietic mesoderm (HM) cells biased towards hematopoietic lineages. We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells. Mechanistically, BMP4 acts as a downstream target of HDAC1, which modulates the expression of BMP4 by deacetylating its enhancer. Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation. In conclusion, our study identifies human HM cells and describes new mechanisms for human hematopoietic development.