Organoid-based single-cell spatiotemporal gene expression landscape of human embryonic development and hematopoiesis

Single-cell level characterization of embryonic development is a major benchmark of human developmental biology. Spatiotemporal analysis of stem-cell-derived embryos offers conceptual and technical advances in the field. Here, we defined the single-cell spatiotemporal gene expression landscape of human embryonic development with stem-cell-derived organoids. We established the human embryonic organoid (HEMO) from expanded potential stem cells and achieved both embryonic and extraembryonic tissues in the same organoid. Time-series single-cell RNA sequencing paired with single-cell resolution spatial revealed human embryonic development signatures such as extraembryonic placenta, yolk sac hematopoiesis neural crest, blood vessels, and cardiac mesoderm. Hematopoietic tissues eventually predominated HEMO with erythropoiesis, mekagaryopiesis, and myelopoiesis. Cell-cell communication network analysis demonstrated that trophoblast-like tissues supplied WNT signaling in neural crest cells to facilitate maturation and migration. Single-cell resolution spatial transcriptomics defined the yolk sac erythro-megakaryopoietic niche. Vitronectin-integrin signaling, a major contributor to megakaryocyte maturation, was predominant in the yolk sac niche in HEMO and to human fetal samples. Overall, our study advances the spatiotemporal analysis of human embryonic development in stem-cell-derived organoids. HighlightsO_LIModeling human embryonic development from stem cells C_LIO_LIUsed of both 10X Chromium and 10X Visium to define the gene expression landscape of embryonic development and hematopoiesis C_LIO_LIWNT signaling as a regulator of neural crest maturation and EMT C_LIO_LIVTN-ITGA2B as the main contributor to Mk maturation within the yolk sac erythro-megakaryopoietic niche C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=158 HEIGHT=200 SRC="FIGDIR/small/505700v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1710d00org.highwire.dtl.DTLVardef@10ca8e0org.highwire.dtl.DTLVardef@2310d1org.highwire.dtl.DTLVardef@252728_HPS_FORMAT_FIGEXP M_FIG C_FIG