Newswise — Around two to three weeks after conception, a crucial stage of development occurs for an embryo. This stage, known as gastrulation, marks the beginning of the transformation of embryonic cells into specialized cells. It triggers a remarkable diversification of cellular types, with the embryonic cells eventually becoming the precursors of various types of cells such as blood, tissue, muscle, and more. Additionally, during this stage, the primitive body axes start to take shape. Understanding this process in the specific context of human development has been a challenging task for biologists. However, recent research has provided an unprecedented opportunity to gain insights into this critical period.
Scientists have adopted a novel approach to address these challenges by utilizing stem cell technologies to model embryo development. Numerous valuable methods have emerged from research groups worldwide. Nonetheless, it is important to note that embryos do not develop in isolation, and previous developmental models have often lacked essential supportive tissues required for embryonic growth. To overcome this limitation, a groundbreaking model has been developed, encompassing both embryonic and extraembryonic components. This comprehensive model enables researchers to investigate the intricate interactions between these two parts during the gastrulation stages. As a result, it provides a unique vantage point to observe the molecular and cellular processes that take place during this critical phase. Furthermore, it offers potential insights into the reasons behind pregnancy failures and the origins of congenital disorders.
The team responsible for this breakthrough includes Berna Sozen, PhD, and Zachary Smith, PhD, who both serve as assistant professors of genetics at Yale School of Medicine (YSM). Their findings were published in the prestigious scientific journal Nature on [tk] (date not provided).
Valentina Greco, PhD, the Carolyn Walch Slayman Professor of Genetics at YSM and incoming president-elect of the International Society for Stem Cell Research (ISSCR), who was not involved in the study, emphasizes the significance of this work in providing an ethical approach to understanding the earliest stages of human growth. According to Greco, the stem cell model developed in this study offers a valuable alternative for investigating aspects of early human development that are typically concealed within the mother's body.
Haifan Lin, PhD, the Eugene Higgins Professor of Cell Biology, director of the Yale Stem Cell Center, and president of ISSCR, commends the Sozen and Smith groups for achieving a significant milestone in developing in vitro models to study the initial stages of human development. Lin stresses the importance of these studies in advancing our understanding of health and disease, acknowledging the ethical considerations involved. He appreciates the researchers' sensitivity to these concerns by restricting the model's ability to further develop.
The ethical implications of this research are profound, with questions arising about the potential of these models to develop into human beings. The principal investigator of the study, Sozen, asserts that they do not possess this capacity. The published paper demonstrates that the model lacks trophectodermal cells, which are necessary for embryo implantation in the uterus. Sozen clarifies that the model represents a developmental stage beyond the timeframe in which embryos can implant. She emphasizes that it is crucial to recognize that their model cannot grow further or implant and, therefore, should not be considered a human embryo. Nonetheless, as a reductionist approach to mimic and study aspects of natural development, the model holds immense potential, particularly in situations where strict guidelines limit scientists' ability to study actual embryos.
New Model Contains Embryonic and Extraembryonic Tissues
The embryos consist of two main components: the embryonic and extraembryonic components. In our adult bodies, the tissues we have developed from the embryonic component, while the extraembryonic component encompasses the supportive tissues responsible for providing nutrition and other forms of support, such as the placenta and yolk sac. Previous models of embryonic development primarily focused on single-tissue models that only included the embryonic component.
However, a recent study led by Yale University introduced a novel approach. The research team cultivated embryonic stem cells in a laboratory setting, generating a new model. These cells were then transferred into a three-dimensional culture system and exposed to specific conditions that stimulated self-organization and differentiation. Consequently, the cells differentiated into two distinct lineages: embryonic and extraembryonic precursors. Notably, the extraembryonic cells in this model served as precursors for the yolk sac.
Over the course of approximately one week, the researchers cultivated these cellular lineages within the culture and closely examined their developmental interactions. The study delved into intricate details, such as the signaling processes between the two lineages and the influence of specific genes on each other. Significantly, this level of mechanistic analysis had been relatively limited in previous scientific literature.
According to Sozen, a member of the research team, their investigation shed light on previously unexplored aspects, expanding the understanding of the cellular interactions and genetic impact during embryonic development.
The Need for Models of Human Development
Although researchers have gained valuable insights from studying embryos of other species, such as mice, the limited availability of human embryos has resulted in significant gaps in our understanding of human development. Sozen emphasizes the importance of examining the human system to truly comprehend human development, stating, "If you want to understand human development, you need to look at the human system." The significance of this new model lies in its direct relevance to our own species, providing crucial information about human development.
This innovative model not only provides access to the critical phase of human development known as gastrulation but also enables a substantial increase in research opportunities. By generating thousands of these models, researchers can conduct extensive analyses that would be impractical with human embryos alone. Sozen acknowledges the collaborative nature of scientific progress, expressing excitement about the collective vision and accomplishments of scientists worldwide. As he puts it, "I'm one scientist with one vision, but thinking about what other scientists are envisioning globally and what we can all accomplish is just really, really exciting to me."
The newly developed model demonstrates an impressive efficiency rate of over 70%, meaning that the stem cells aggregate correctly in approximately 70% of the cases. However, the authors acknowledge certain limitations in the approach, making it challenging to directly compare some of their findings with natural embryos. Sozen expresses her intention to continue refining the models to enhance their standardization in future research.
The research team firmly believes that these models will revolutionize scientists' understanding of human developmental biology. In their recent publication, the team delved into the molecular pathways involved in the onset of human gastrulation. They aim to conduct further investigations that explore developmental pathways in greater depth, including the potential connection between pregnancy loss, congenital disorders, and failures during gastrulation stages. Sozen anticipates that her model can be utilized to examine these disorders and gain insights into the underlying issues. She explains, "Previous model systems have explored this aspect to some extent, but our unique model stands out because of its additional tissue, enabling us to delve deeper into the analysis."
By utilizing this advanced model, researchers can delve into the molecular intricacies of human gastrulation and gain a deeper understanding of its implications for pregnancy loss and congenital disorders. The team's ongoing work and future studies hold the promise of uncovering crucial insights into the intricate processes of human development.
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