Simplifying cell fate map by determining lineage history of core pathway activation during fate specification

A fundamental question in developmental biology is how a single genome gives rise to the diversity of cell fates. In essence, each cell fate in the human body is a unique but stable output state of the genome, maintained by positive and negative feedbacks from both inside and outside the cell (a stable cell state). Traditionally, defining a cell fate means identifying a unique combination of transcriptional factors expressed by the specific cell type. The hundreds of transcriptional factors in the genome, however, have complicated the task of simplifying cell fate representation and obtaining insights into its regulation. Moreover, results from this approach provides only a mostly static picture, with each cell fate/state disconnected from one another. An alternative approach instead defines cell fates by determining their relationship to each other, through identifying the signaling pathways that control each step of their lineage transition from a common progenitor during development. Decades of studies have shown only a handful of signaling pathways are sufficient to specify all cell fates in the body, simplifying the execution of such a strategy. In this review, I will argue this alternative approach is not only feasible but also has the potential of simplifying the cell fate landscape as well as facilitating the engineering of different cell fates for regenerative medicine.