Cellular Reprogramming in Bursts and Phases

Abstract

As a biochemical process, direct cellular reprogramming is slow and complex. The early stages of this process is the most critical determinant of successful phenotypic conversion. This study provides insight into the statistical signatures that describe temporal structure in the reprogramming process. We examine two sources of variation in reprogramming cells: clonal instances from various tissues of origin and rate of expansion between these lines. Our analytical strategy involved modeling the potential of populations to reprogram, and then applying statistical models to capture this potential in action. This two-fold approach utilizes both conventional and novel techniques that allow us to infer and confirm a host of properties that define the phenomenon. These results can be summarized in a number of ways, and essentially suggest that reprogramming is organized around changes in gene expression phenotype (phases) which happens sporadically across a cellular population (bursts).