Intestinal motility refers to a stage that most animal embryos undergo during development. Researchers from Institute of Zoology, Chinese Academy of Sciences, Beijing Institute of Stem Cell and Regenerative Medicine and China Agricultural University reconstructed the first complete human gastrula model with digital 3D for the first time. On April 23rd, the related research results were published in Cell with the title of 3D Reconstruction of a Gaserating Human Embryo.

In the early 20th century, scientists divided the first eight weeks of human embryonic development into 23 Carnegie stages (CS1-CS23). Intestinal motility mainly occurs in the CS7-CS8 stage. At this stage, the blastocyst with only one layer of cells undergoes recombination, forming a structure consisting of three embryonic layers (i.e. ectoderm, mesoderm, and endoderm), and the newly formed three embryonic layer cells combine and coordinate to develop into various organs. Each embryonic cell can develop into specific organs and tissues.

Due to bioethical considerations, the in vitro culture of human embryos is limited to 14 days, known as the "14 day rule.". The movement of the human gut occurs between 14 and 21 days after fertilization, and is considered the "black box" of human development. Although embryonic structures constructed based on pluripotent stem cells in vitro can help scientists understand this process to some extent, due to technological limitations, currently embryonic structures cannot fully reflect the developmental trajectory of embryos. Therefore, studying the developmental landscape of embryonic motility in natural conditions is of great clinical significance for exploring the pathogenesis of miscarriage and fetal diseases caused by early embryonic developmental abnormalities, and is expected to provide a blueprint for constructing in vitro embryo like models.

This study is based on a precious CS8 stage complete human embryo, using continuous cross-sectional high-resolution spatial transcriptome slices and combining machine learning algorithms for 3D alignment, constructing a 3D spatial distribution point cloud map of different cell types and gene expression in the complete embryo, and then digitally reconstructing the complete human intestinal embryo model in 3D.

Research has found that through 3D reconstruction of human intestinal embryos, the relative distribution position of each type of cell in the embryo can be accurately seen. By combining spatial location information with cell group information and gene expression information, research can more accurately define different cell types and analyze their interaction with surrounding cells. Taking the formation of mesodermal cells as an example, the migration process of the mesoderm is currently unclear. This study utilized 3D reconstruction of embryos and analyzed them based on spatial location and characteristic genes. It was found that various subpopulations of mesoderm, such as axial mesoderm, paraxial mesoderm, intermediate mesoderm, lateral mesoderm, and precursor cells of extraembryonic mesoderm, were arranged along the direction from head to tail in the original position. This indicates that the mesoderm may have undergone cell fate determination before migrating out of the original stem, and migrate to the corresponding position based on the predetermined fate. This fills the knowledge gap in the development of various cell lineages in human embryos during the gastrula stage.

Furthermore, the spatial position information reconstructed in 3D allows scientists to explore another important event in the process of intestinal motility, which is the formation of the body axis. The body of mammals has three body axes, namely the head tail axis, the back abdomen axis, and the left right axis, along which various tissues and organs are arranged in order. During the embryonic development of vertebrates, it mainly relies on the action of a type of cell called the tissue center, which gradually establishes the three body axes of the body. This study focused on seven important cellular signaling pathways during development, integrated spatial distribution information, and analyzed the expression of signal ligands and receptors during the axial establishment process. Research has found that during this period, there may be a tissue center at the tail of human embryos similar to the central notochord, opening up a new door for exploring the development of very early human embryos.



In addition, in order to facilitate readers' understanding and use, the team has established and published an interactive sharing website（ http://www.cs8.3dembryo.com ）.



The research work has received support from the national key research and development plan.



Paper link:论文链接





3D reconstruction of early human CS8 embryos. A is the CS8 embryonic structure and spatial transcriptome sequencing process; B represents the 3D reconstructed point cloud and pattern maps