Chinese researchers have uncovered the cellular origin, differentiation pathways and species-specific features of human primitive hematopoiesis, filling a theoretical gap in understanding the developmental rules that operate just before the onset of human gastrulation.

The findings, by researchers from the Institute of Hematology & Blood Diseases Hospital at the Chinese Academy of Medical Sciences (IHCAMS), Beijing Institute of Technology, and the Chinese PLA General Hospital, were recently published online in the journal Nature.

Gastrulation is a critical phase in human embryonic development and one of the most mysterious and fascinating chapters in life sciences. During this stage, the embryo transforms from a simple two-layered structure into a complex three-layered architecture, establishing its body axis while undergoing multilineage differentiation and the formation of organ primordia.

It was previously believed that blood cells emerged only after gastrulation. However, by studying a rare early-stage human embryo sample, the team discovered that human hematopoiesis begins much earlier than previously thought. Even before the formal initiation of gastrulation, the hematopoietic "factory" in the embryonic yolk sac is already active, producing primitive erythrocytes, primitive megakaryocytes, and myeloid progenitor cells.

The researchers also constructed the first high-resolution spatial transcriptomic atlas of the pre-gastrulation stage. Their work revealed that the earliest human blood cells do not originate from the epiblast, as traditionally assumed, but instead derive from the extra-embryonic mesoderm, which itself arises from the hypoblast. This finding settles a long-standing debate over the origin of early human hematopoietic cells.

Furthermore, the embryonic yolk sac is not a functionally uniform hematopoietic site. It contains two distinct "workshops" with different locations and functions: one primarily generates myeloid progenitor cells, while the other predominantly produces primitive erythrocytes and primitive megakaryocytes.

The study not only reshapes the understanding of early human hematopoiesis but also provides physiological benchmarks and fresh conceptual insights for research areas such as de novo regeneration of blood cells in vitro and the study of early human developmental abnormalities, said Lan Yu, a researcher at the IHCAMS.