Small intestinal stem cell markers

Abstract

Stem cells hold great promise for regenerative medicine but remain elusive in many tissues, including the small intestine, where it is well accepted that the epithelium is maintained by intestinal stem cells located in the crypts. The lack of established markers to prospectively identify intestinal stem cells has necessitated the use of indirect analysis, e.g. long-term label retention, which is based on the hypothesis that intestinal stem cells are slow-cycling. Several intestinal stem cell markers have been proposed, including Musashi-1, BMPR1alpha, phospho-PTEN, DCAMKL1, Eph receptors and integrins, but their validity, using functional and/or lineage tracing assays, has yet to be confirmed. Recently, Lgr5 has been identified by lineage tracing as an intestinal stem cell marker. In this review we summarize what is known about the currently reported intestinal stem cell markers and provide a rationale for developing model systems whereby intestinal stem cells can be functionally validated.

Fig. 1

Schematic Illustration of the location of putative small intestinal stem cell markers. (A) Numbers of long-term label-retaining cells, plotted against cell position in the crypt, indicated by numbers on the left. (B) Expression pattern of cell membrane proteins, EphB2, EphB3, and the Ephrins B1 and B2. (C) Location of cells expressing cytoplasmic Musashi1 (MSI1) (purple) or nuclear HES (orange). On right, expression pattern of integrins. (D) Location of cells expressing BMPR1a (blue), P-PTEN (red), DCAMKL1 (purple), telomerase (green) and Lgr5/GPR49 (yellow).