OLFM4 Is a Robust Marker for Stem Cells in Human Intestine and Marks a Subset of Colorectal Cancer Cells

The epithelium of the small intestine and colon is the most rapidly self-renewing tissue in mammals. Proliferative cells are confined to crypts, and differentiated cell types predominantly occupy the villi in the small intestine and the surface epithelium in the colon. We recently demonstrated the existence of a long-lived pool of cycling stem cells defined by Lgr5 expression. These cells are intermingled with postmitotic Paneth cells at crypt bottoms in the small intestine. In the colon, they reside at crypt bottoms and are intermingled with goblet cells. Whereas knockin alleles of Lgr5 have been instrumental in defining these cells, Lgr5 mRNA or protein levels are too low to serve as faithful markers. Olfactomedin-4 (Olfm4) has emerged from a gene signature for these Lgr5 stem cells as a robust marker for murine small intestinal stem cells. Herein, we show that OLFM4 is highly expressed in crypt base columnar cells in human small intestine and colon. Moreover, OLFM4 is expressed in cells within adenocarcinomas of the colon. We propose that OLFM4 can serve as a useful marker for Lgr5-type stem cells in human small intestine and colon.