Programming Morphogenesis through Systems and Synthetic Biology

Stem cell-derived multicellular systems and organoids have opened new opportunities to emulate and understand human development in vitro and provide novel patient specific tissue surrogates for disease modeling. Single cell sequencing technologies and spatial tissue analysis provide a wealth of information on cellular fate and function and offer invaluable opportunities to decipher developmental processes. Mammalian synthetic biology utilizes designer synthetic gene circuits to program cell fate and functions towards a desired outcome. Engineering morphogenesis is an emerging area of science that integrates engineering principles with developmental biology to control and guide collective cell behaviors. Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell–cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell–cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. nucleic acid or peptide molecule that binds a particular molecular target with high affinity and specificity. aptamer domain fused to a ribozyme domain. Upon the binding of the aptamer, catalytic action of the ribozyme region is activated. technique used for visualizing specific sequences of nucleic acids within cells based on complementary base pairing of a florescent or radioactively tagged DNA probe with a target sequence. starting with high-level model that establishes the goals and functions of a system before its physical design or construction. stem cell-based model that emulates spatiotemporal aspects organization and differentiation of gastrulation. network of interacting genes that collectively controls particular cellular functions. partly analogous to electronic circuits, it is used in synthetic biology to define an integrated assembly of genetic parts that produces a genetic function. defined broadly here as events that collectively encode tissue pattern and shapes that are controlled by cell fate decisions, migration, cell–cell interaction and physical cues. here it refers to engineering morphogenesis using genetic techniques. in vitro approaches directed towards generation of complex tissues and organ-like structures via emulating aspects of developmental processes. self-organizing, 3D, multicellular system grown from stem cells in vitro that contains several organ-specific cell types with associated tissue structures and functions. decomposition of a system into its functional parts in order to guide understanding of performance objectives and functions of individual components. loosely defined as spontaneous formation of ordered structures via local interactions of less organized parts with no centralized ordering or external template. interdisciplinary field of study for engineering biology that entails (re)design and construction of existing or novel biological systems using well-characterized standardized genetic parts. interdisciplinary field of study that aims to develop an integrated understanding of biological systems using quantitative measures of individual components, their interaction dynamics and computational modeling.