Cell function manifests through intricately controlled dynamic processes that both interact amongst each other—in a network—and also respond to external signals, eg, transcription factors, etc. Recently, controllability of complex networks has received considerable attention for its potential to influence the behavior of dynamically interacting nodes of interest in biological, social, and engineered networks. For example, Liu et al. recently used the notion of structural controllability to provide insights into the percentage of nodes required to control the evolution of the state of the nodes in a network in response to external stimuli [1–3]. However, when applying the notion of controllability in biology, we must consider the dynamical nature of biological systems as well as the timing of the external input. Here, we provide a parallel yet distinct approach to the problem of network controllability in the context of cell differentiation and highlight the importance of network controllability and its applications in dynamical biological systems [4].

Cellular differentiation is the process via which the nucleus achieves a new function. After many years of intensive investigation, we are just scratching the surface of how the cell nucleus functions on a global level to produce specialized cell types. The relationship between nuclear form and function will be critical to understanding the dynamics of the nucleus during cell differentiation [5, 6]. We argue that feedback between form and function during differentiation fine-tunes a cellspecific form, leading to the desired function [7]. In this venue, we first define form as a geometric network that reflects the physical configuration of chromosomes in the interphase nucleus and function as the transcriptional network. Adopting this geometric point of view allows us to consider the evolution of a concrete, physically realizable network during differentiation, and assess how essential features of this network evolve over time. The basic question is thus how network geometry with a particular initial configuration evolves toward a specific cell type