Projects responsive to this solicitation must aim to establish a robustly validated and reproducible set of differentiation design rules, mechanistic models, real-time sensing, control, and quality assurance methods, and integrate them into a workable differentiation strategy. They must deepen our fundamental understanding of how cells develop and differentiate, providing insights into mechanisms, molecular machinery, dynamics, and cell-cell and cell-extracellular matrix (ECM) interactions, and use this understanding to manipulate cells purposefully.