Figure 1: Cardiac Fibroblast Movement in Cell State Space.

Cardiac fibroblasts have long been thought to exist on a linear continuum between an unactivated state and a fibrotic matrix secreting myofibroblast state. This figure depicts a more complete picture of cardiac fibroblast “state space.” State transition may be reversible indicated by the bidirectional arrow heads, new fibroblasts cell states may exist (e.g. matrifibrocytes), and transdifferentiation directly between these states might be possible indicated by dotted lines. Importantly the third dimension of state space “activation energy” is critical to understanding this concept. For example, the myofibroblast state could be unstable and not in a deep valley, indicating that a small amount of activation energy could induce a state change. In contrast, a more permanent cell state, like a cardiomyocyte, would have a much deeper valley to represent low likelihood of state transition. Known gene expression markers of the fibroblast states shown are listed, however it is important to note that a position in multidimensional state space is far more complex than a small number of marker genes.