Little is known about the molecular and cellular events that occur during early embryonic development in primate species. Now, an internationally renowned team of scientists has created a method to allow primate embryos to grow in the laboratory longer than ever before, enabling the researchers to obtain molecular details of key developmental processes for the first time. This research, while done in nonhuman primate cells, can have direct implications for early human development.
The findings, published in Science, provide valuable insight into early embryonic development and potentially can help inform approaches to advance regenerative medicine in humans.
"Our study provides a first look into this black box of early development," says co-corresponding author. "We can now observe how cells progress through each embryonic stage and what factors they need to develop, which will aid in creating better options for the generation of a variety of cells and tissues."
"To understand cellular and molecular mechanisms underlying primate gastrulation, we began monkey embryo culture experiments in China three years ago. Because of the team's long-standing expertise on the systematic study of nonhuman primates and well-established reproductive research systems, such as an in vitro fertilization platform, we succeeded in achieving our goals. This can help to shed light on previously unknown aspects of human post-implantation development." says the other co-corresponding author.
The scientists wanted to study an early developmental milestone called gastrulation, which occurs when a developing embryo transforms into a multilayered structure, called the gastrula, from which all future tissues and organs will be derived. One layer will become the lungs, gastrointestinal tract and liver; another will become the heart, muscles and reproductive organs; and a third will become the skin and nervous system. Yet, scientists did not know the molecular and cellular drivers of this process in primates, largely due to limited access to early embryos.
"Our goal was to culture a primate embryo from an early timepoint in order to study the process of development," says a co-author of the paper. "We wanted to monitor the embryos every day to observe their shape, size and migration patterns as well as how they generate different types of cells during early primate development."
To better study this critical transformation, the scientists modified a previously established embryo culture protocol to allow an early primate embryo to develop in laboratory conditions for up to twenty days; previously researchers had only been able to maintain cultured primate embryos prior to the second week of gestation. Using the new protocol, the team found that the cells within cultured embryos exhibited clear developmental trajectories towards each layer of the gastrula, and the results revealed some of the molecular details required for this growth. Cultured embryos underwent key primate developmental stages, including lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and primordial germ cell-like cell (PGCLC) differentiation.
Single-cell RNA sequencing analysis revealed development trajectories of primitive endoderm, trophectoderm, epiblast lineages, and PGCLCs. Analyzing single-cell chromatin accessibility identified transcription factors specifying each cell type.
The data could also be used as a resource to aid in extending the cultured embryo duration past twenty days in order to better study stem- cell differentiation (specialization).
"These results illuminate some of the regulation networks and signaling pathways that are crucial to development in primates," says the co-corresponding author. "This system provides a foundation and resource for developing better strategies to examine early primate development in both health and disease, in the laboratory."
Culturing primate embryos to learn more about human development
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