scRNA-seq and CITE-seq of yolk sac cell reveals multiorgan functions during human early development

The yolk sac (YS) is a membranous structure attached to the developing embryo that acts to support hematopoiesis, metabolism, and coagulation. Our current understanding of its role in human development has been limited by a reliance on nonhuman model systems. A team led by researchers at the Wellcome Sanger Institute used single-cell RNA sequencing, light-sheet microscopy, and RNAscope-based in situ hybridization to generate a human YS atlas derived from 10 samples spanning 4 to 8 postconception weeks or Carnegie stages 10 to 23. The researchers found that endoderm in human YS, but not murine YS, provides hematopoietic growth factors. Furthermore, in humans, the YS is the dominant source of early erythropoiesis, unlike in mice, in which the liver also plays a role. Finally, the authors report that human YS can fuel the accelerated production of macrophages from hematopoietic stem and progenitor cells independently of monocytes.

Multiorgan functions of the human YS

Researchers characterized functions of the developing human YS, combining scRNA-seq and CITE-seq with 2D and 3D imaging techniques. Thier findings revealed YS contributions to metabolic and nutritional support and to early hematopoiesis. They characterized myeloid bias in early hematopoiesis, distinct myeloid differentiation trajectories, evolutionary divergence in initial erythropoiesis, and YS contributions to developing tissue macrophages. Met., metabolic; Coag., coagulation; Mac, macrophage.