SPATIO-TEMPORAL EXPRESSION PROFILE OF STEM CELL-ASSOCIATED GENE LGR5 IN THE INTESTINE DURING THYROID HORMONE-DEPENDENT METAMORPHOSIS IN XENOPUS LAEVIS. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5 or Gpr49) is a well-established stem cell marker in the adult mouse intestinal crypt. We have cloned and analyzed the spatiotemporal expression profile of LGR5 gene during frog metamorphosis. We showed that the two duplicated LGR5 genes in Xenopus laevis and the LGR5 gene in Xenopus tropicalis are highly homologous to the LGR5 in other vertebrates. The expression of LGR5 is induced in the limb, tail, and intestine by TH during metamorphosis. More importantly, LGR5 mRNA is localized to the developing adult epithelial stem cells of the intestine. These results suggest that LGR5-expressing cells are the stem/progenitor cells of the adult intestine and that LGR5 plays a role in the development and/or maintenance of the adult intestinal stem cells during postembryonic development in vertebrates. AN ESSENTIAL AND EVOLUTIONARILY CONSERVED ROLE OF PROTEIN ARGININE METHYLTRANSFERASE 1 FOR ADULT INTESTINAL STEM CELLS DURING POSTEMBRYONIC DEVELOPMENT. Adult stem cells are essential for the development of adult organs and tissue repair and regeneration. The intestine is an excellent organ for studying adult stem cells as the intestinal epithelium, the tissue responsible for the food processing and nutrient absorption, is continuously renewed through stem cell division followed by cell differentiation and eventual death of the differentiated cells throughout adult life in vertebrate. Intestinal remodeling during TH-dependent metamorphosis of the South African frog (toad) Xenopus laevis offers a unique opportunity to study adult stem cell development and proliferation. We have shown that TH receptor (TR) is both necessary and sufficient for mediating the effects of TH on intestinal development and that TR recruits coactivator complexes to control metamorphosis. We have now shown that the TR-coactivator PRMT1 (protein arginine methyltransferase 1) is upregulated in a small number of larval epithelial cells and that these cells dedifferentiate to become the adult stem cells. More importantly, our in vivo studies showed that PRMT1 plays an evolutionally conserved role in the development of adult intestinal stem cells. These findings are not only important for the understanding of organ-specific adult stem cell development but also have important implications in regenerative medicine of the digestive tract.
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