Figure 6
BET bromodomain function in intestinal stem cell differentiation.
A schematic representation of the differentiation of Lgr5-expressing stem cells into each of the secretory cell types. Lgr5 + stem cells differentiate into Atoh1 + cells, a precursor for enteroendocrine (E), goblet (G) and Paneth (P) cells. Atoh1 + cells form goblet and Paneth cells though a pathway involving Spdef-expressing TA cells (TAG/P). Enteroendocrine cells are derived from Atoh1 + cells through an Ngn3-dependent intermediate (TAE). The activity of BET bromodomains is required for the formation of TAE cells, or the proper expression of Ngn3 within this cell population. There are conflicting studies that describe Lgr5 + cells forming tuft cells (T) through pathways that are dependent and independent of an Atoh1 + intermediate. The uncertain lineage of tuft cells is represented by dashed lines. Gfi1B is expressed in both TA cells destined for tuft cell formation (TAT) as well as fully differentiated Dclk1-expressing tuft cells. BET bromodomain activity is likely required for the differentiation of TAT cell into mature tuft cell.
