In toto biological framework: Modeling interconnectedness during human development

Abstract

Recent advancements in pluripotent stem cell and synthetic tissue technology have brought significant breakthroughs in studying early embryonic development, particularly within the first trimester of development in humans. However, during fetal stage development, investigating further biological events represents a major challenge, partly due to the evolving complexity and continued interaction across multiple organ systems. To bridge this gap, we propose an “in toto” biological framework that leverages a triad of technologies: synthetic tissues, intravital microscopy, and computer vision to capture in vivo cellular morphodynamics, conceptualized as single-cell choreography. This perspective will discuss the inherent challenges in capturing such complexities and explore engineering technologies to delve into the less-explored phase of human development. We also propose reframing the organ-centric to a system-centric paradigm, as such a framework broadens the value of the in vivo-embedded synthetic-tissue-based approach for interrogating the multifaceted interplay of human developmental processes during this crucial stage.