Role of HOX Genes in Stem Cell Differentiation and Cancer

Figure 3

HOX gene expression during colonocyte differentiation. Normal colonic crypts consist of mainly three types of cells based on their location in the crypt. Colon stem cells (SCs) reside at the base of the colonic crypt (shown in blue color). HOXA4, HOXA9, and HOXD10 are expressed in colonic SCs and regulate colonic crypt SC differentiation [49, 50]. SCs generate transit-amplifying cells (shown in green color) that are actively proliferating and differentiating (shown in gold-bronze yellow color) as they move up the axis in the colonic crypt. Finally, fully differentiated or terminally differentiating cells are found at the top of the crypt (shown in brown color). Studies have shown that HOXA family genes are expressed mostly in proliferating colonic cells, and HOXC family genes are expressed in differentiating cells [68]. HOXB and HOXD family genes are expressed throughout the colonic crypts [68]. In colon tumors, the dysregulation of HOXA4 and HOXA9 in colon SCs caused aberrant self-renewal and proliferation, contributing to colon carcinoma [50]. HOXC8 and HOXC9 are expressed in the differentiating cells in the colonic crypt [68].