Int J Biol Sci 2012; 8(8):1217-1224. doi:10.7150/ijbs.5109 This issue


Thyroid Hormone Regulation of Adult Intestinal Stem Cell Development: Mechanisms and Evolutionary Conservations

Guihong Sun1✉, Yun-Bo Shi2✉

1. Key Laboratory of Allergy and Immune-related Diseases and Centre for Medical Research, School of Medicine, Wuhan University, Wuhan 430072, P.R. China.
2. Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., Bethesda, Maryland, 20892.

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Sun G, Shi YB. Thyroid Hormone Regulation of Adult Intestinal Stem Cell Development: Mechanisms and Evolutionary Conservations. Int J Biol Sci 2012; 8(8):1217-1224. doi:10.7150/ijbs.5109. Available from

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The adult mammalian intestine has long been used as a model to study adult stem cell function and tissue renewal as the intestinal epithelium is constantly undergoing self-renewal throughout adult life. This is accomplished through the proliferation and subsequent differentiation of the adult stem cells located in the crypt. The development of this self-renewal system is, however, poorly understood. A number of studies suggest that the formation/maturation of the adult intestine is conserved in vertebrates and depends on endogenous thyroid hormone (T3). In amphibians such as Xenopus laevis, the process takes place during metamorphosis, which is totally dependent upon T3 and resembles postembryonic development in mammals when T3 levels are also high. During metamorphosis, the larval epithelial cells in the tadpole intestine undergo apoptosis and concurrently, adult epithelial stem/progenitor cells are formed de novo, which subsequently lead to the formation of a trough-crest axis of the epithelial fold in the frog, resembling the crypt-villus axis in the adult mammalian intestine. Here we will review some recent molecular and genetic studies that support the conservation of the development of the adult intestinal stem cells in vertebrates. We will discuss the mechanisms by which T3 regulates this process via its nuclear receptors.

Keywords: adult organ-specific stem cell, histone methyltransferase, transcriptional coactivator, thyroid hormone receptor, dedifferentiation, Xenopus laevis, metamorphosis.