Figure 3.

Conceptual Overview of GERD-Induced Cellular Reprogramming in the Pathogenesis of Barrett’s Metaplasia. Potential pathways for the origin of Barrett’s metaplasia include (A) Direct transdifferentiation is the process in which an individual, fully differentiated cell (i.e. squamous) change directly into another type of fully differentiated cell (i.e. intestinal-type cell) in the setting of GERD. (B) Transdifferentiation in the setting of GERD may result in de-differentiated cells with features of both squamous and intestinal cell types (transitional cells). If GERD subsides, this transitional cell can re-differentiate into a squamous cell. If GERD continues, this transitional cell can reprogram into the new intestinal-type cell through a series of intervening cell divisions. (C) Transcommitment is the process in which immature progenitor cells are reprogrammed in the setting of GERD to give rise to the gastric and intestinal cell types that comprise Barrett’s metaplasia. Progenitor cells that are native to the esophagus undergo reprogramming to columnar gastric-type cells. Some of these gastric-type columnar cells undergo further reprogramming into intestinal-type cells. Progenitor cells may migrate from the proximal stomach into the esophagus, but some of these gastric progenitor cells would still have to undergo reprogramming into intestinal-type cells. Some of the transcription factors that have been implicated in these GERD-induced reprogramming processes are indicated in blue.