Interconversion Between Intestinal Stem Cell Populations in Distinct Niches

• Published in: Science (American Association for the Advancement of Science) Vol. 334; no. 6061; pp. 1420 - 1424
• Main Authors: Takeda, Norifumi, Jain, Rajan, LeBoeuf, Matthew R., Wang, Qiaohong, Lu, Min Min, Epstein, Jonathan A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 09.12.2011; The American Association for the Advancement of Science
• Subjects: Animals; Biological and medical sciences; Cell Cycle; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells; Cells, Cultured; Crypts; Cultured cells; Descendants; Endocrine cells; Epithelial cells; Epithelial Cells - cytology; Fundamental and applied biological sciences. Psychology; Homeodomain Proteins - analysis; Homeodomain Proteins - genetics; Intestinal Mucosa - cytology; Intestinal Mucosa - drug effects; Intestine, Small - cytology; Intestine, Small - drug effects; Intestine. Mesentery; Intestines; Mice; Models, Biological; Multipotent Stem Cells - cytology; Multipotent Stem Cells - physiology; Neural stem cells; Organoids; Paneth Cells - cytology; Stem Cell Niche; Stem cells; Tamoxifen - pharmacology; Vertebrates: digestive system; Interconversion; Digestive system; Stem cell; Rodentia; Gut; Vertebrata; Mammalia; Lieberkuhn gland; Mouse; Animal; Genetics; Epithelial cell; Homeobox gene
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1213214

Intestinal epithelial stem cell identity and location have been the subject of substantial research. Cells in the +4 niche are slow-cycling and label-retaining, whereas a different stem cell niche located at the crypt base is occupied by crypt base columnar (CBC) cells. CBCs are distinct from +4 cells, and the relationship between them is unknown, though both give rise to all intestinal epithelial lineages. We demonstrate that Hopx, an atypical homeobox protein, is a specific marker of +4 cells. Hopx-expressing cells give rise to CBCs and all mature intestinal epithelial lineages. Conversely, CBCs can give rise to +4 Hopx-positive cells. These findings demonstrate a bidirectional lineage relationship between active and quiescent stem cells in their niches.