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Understanding of early human development is hampered by a lack of reference datasets from natural embryos, especially those with spatial information at key stages such as gastrulation. On April 23, 2024, Prof. Leqian Yu and Prof. Jingtao Guo from the Institute of Zoology of the Chinese Academy of Sciences and the Beijing Institute of Stem Cell and Regenerative Medicine, Prof. Yulei Wei from China Agricultural University and Dr. Xiaoyan Wang from the Institute of Zoology, Chinese Academy of Sciences jointly published a research paper entitled "3D reconstruction of a gastrulating human embryo" online in Cell. 8 high-resolution spatial transcriptomic analysis was performed at 38,562 points in 62 cross-sections of human embryos. From this spatial transcriptome dataset, the study constructed a 3D model of the CS8 embryo, in which a series of cell subtypes were identified along the anterior-posterior, medial-medial, and dorsoventral axes of the embryo based on gene expression patterns and location information. The study further describes the lineage trajectories of embryonic and extraembryonic tissues, as well as the associated regionalization of regulatory and signaling centers, as well as the signaling activity that supports lineage progression and tissue patterns during gastrulation. The findings of this study provide insights into gastrulation and postgastrulation in human embryos.
gastrulation is the transformation of the double-layered embryonic disc within the blastocyst into a complex multi-dimensional structure, known as gastrulation. This complex event lays the foundation for different cell lineages and spatial patterns. Human gastrulation occurs on days 14 to 21 (E14-21) of the embryo after fertilization, corresponding to the Carnegie stage (CS) 7 to 9. During this period, the ectoderm (Epi) is assigned to the primary germ layer and precursors and derivatives of the extraembryonic tissue. In addition to determining cell lineages, establishing the somatic axis is essential to coordinate patterns of migration, localization, and differentiation of cells. Dynamic signaling centers, such as the notochord, regulate the establishment of body axes, guiding cells to develop towards their designated destinations. This disruption of coordination can lead to serious congenital anomalies. However, the study of human embryogenesis presents unique challenges, as the scarcity of early human embryonic material in utero limits direct study. As a result, researchers' understanding of human gastrulation relies heavily on data from other sources. Animals, such as mice, are the main source of knowledge about gastrulation. In particular, the application of single-cell RNA sequencing (scRNA-seq) provides an increasingly detailed view of developmental gene expression and developmental pathways for each lineage. However, the uniqueness of primate embryos in terms of anatomy, developmental time, and lineage fate determines makes it difficult to understand primate embryos by relying solely on model animals. In vitro primate blastocyst culture methods and pluripotent stem cell-based embryo models developed in recent years have enabled researchers to study the ontogenesis of embryonic lineages outside the womb and reveal several developmental milestones in early primate embryos. However, due to the lack of relevant literature, there are certain difficulties in whether these stem cell-derived embryonic models can faithfully replicate embryonic development.
模式图（Credit: Cell）
For primate embryos in utero, recent transcriptomic characterization of early gastrulation-based human embryos (CS7) and cynomolgus monkey gastrulation-developing embryos has provided important insights into primate gastrulation embryogenesis. Despite these advances, these datasets lack spatial localization information, which makes accurate annotation of cell subtypes challenging. The question of how cell fate is determined in different positions during gastrulation and how the various subtypes of cells coordinate and develop along the axis of the body remains fragmented. In recent years, spatial analysis of marmoset embryos has been performed at the CS5 to CS7 stages after embryo implantation. In this study, laser capture microdissection combined with Smart-seq2 identified important developmental events. The study performed sequential cross-sections of 62 slices of a complete gastrulation CS8 embryo, which allowed the researchers to combine the spatial transcriptome of all slices from anterior to posterior flank, resulting in a complete 3D reconstruction of the embryo. This dataset provides an opportunity to study the basic cellular and molecular signatures of human gastrator-forming events and provides valuable information for the development of advanced stem cell-derived human embryonic models.
Original link https://www.cell.com/cell/abstract/S0092-8674 (24)00357-X#%20
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文章来源|“ iNature"
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