Epiblast diversification and blood formation in a human pregastrula.
basic_science · Level V
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- Record sourced from PubMed, PMID 42343132.
- Also identified by DOI 10.1038/s41586-026-10698-y.
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Abstract
The incipient stage of gastrulation in human, when the primitive streak is about to emerge, represents a critical yet underexplored period. Here we present the high-resolution spatial transcriptomic landscape of a human embryo at Carnegie stage 6 (approximately 13-14 days post-conception), a stage at which primitive streak remains invisible and gastrulation-derived mesodermal/endodermal progenitors are not yet transcriptomically detected. We identified an anterior visceral endoderm-like hypoblast population, as well as a trifurcated developmental trajectory of the epiblast, progressing towards the amnion, primitive streak and node/prechordal plate/notochord (axial mesoderm) at subsequent developmental stages<sup>1-3</sup>. Furthermore, our findings challenge the existing paradigms by revealing that primitive haematopoiesis, involving three blood lineages, initiates in human yolk sac before gastrulation, earlier than previously recognized<sup>2,4-7</sup>, and that the first blood cells arise from the extra-embryonic mesoderm with a hypoblast rather than epiblast origin. Notably, we identified two spatial zones, each consisting of molecularly distinct yolk sac endoderm and extra-embryonic mesoderm populations, that respectively facilitated the generation of erythro-megakaryocytic lineages and myeloid precursors. These findings provide insights into the onset of gastrulation and the earliest blood formation in humans, with profound implications for advancing stem cell-derived human embryo models and in vitro blood regeneration.