Magic embryology: yoke sac functions (Introduction)

by David Turell , Friday, August 18, 2023, 20:20 (463 days ago) @ David Turell

Multiple:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/18_august_2023/4124...

"The yolk sac (YS) generates the first blood and immune cells and provides nutritional and metabolic support to the developing embryo. Our current understanding of its functions derives from pivotal studies in model systems, and insights from human studies are limited. Single-cell genomics technologies have facilitated the interrogation of human developmental tissues at unprecedented resolution. Atlases of blood and immune cells from multiple organs have been greatly enhanced by focused, time-resolved analyses of specific tissues.

" To characterize the functions of the human YS, we performed single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) on the YS and paired embryonic liver. After integration with external datasets, our reference comprised 169,798 cells from 10 samples spanning 4 to 8 postconception weeks PCW) or Carnegie stages (CS) 10 to 23. A repertoire of two-dimensional (2D) and 3D imaging techniques provided spatial context and validation. We compared the products of two hematopoietic inducible pluripotent stem cell (iPSC) culture protocols against our reference.

"We determined that YS metabolic and nutritional support originates in the endoderm and that the endoderm produces coagulation proteins and hematopoietic growth factors [erythropoietin (EPO) and thrombopoietin (THPO)]. Although metabolic and coagulation protein production was conserved among humans, mice, and rabbits, EPO and THPO production was observed in humans and rabbits only.

"We reconstructed trajectories from the YS hemogenic endothelium to early hematopoietic stem and progenitor cells (HSPCs). Using transcriptomic signatures of early and definitive hematopoiesis, we parsed YS HSPCs into myeloid-biased early HSPCs and lymphoid and megakaryocyte-biased definitive HSPCs. Human embryonic liver remained macroscopically pale before CS14, when hematopoietic cells first emerge from the aorta-gonad-mesonephros (AGM) region. Tracking hemoglobin (Hb) subtypes led us to conclude that initial erythropoiesis is YS restricted. By contrast, in mice, Hb subtypes suggested two waves of pre-AGM erythropoiesis, including maturation in the macroscopically red embryonic liver.

"Before CS14, monocytes were absent and macrophages originated from HPSCs via a premacrophage cell state. After CS14, monocytes emerged and a second, monocyte-dependent differentiation trajectory was reconstructed. A rare subset of TREM2+ macrophages, with a microglia-like transcriptomic signature, was present after CS14. The iPSC system optimized for macrophage production recapitulated the two routes to macrophage differentiation but did not generate the diversity of macrophages (including TREM2+ macrophages) observed in developing tissues.

"CONCLUSION: Our study illuminates a previously obscure phase of human development, where vital functions are delivered by the YS acting as a transient extraembryonic organ."

Comment: The developing fertilized egg ends up by creating an invasive placenta with its own plethora of functions. Not by chance.