Université de Strasbourg, Inserm, IRFAC/UMR-S1113, FMTS, 3 Avenue Molière 67200, Strasbourg, France.
Cell Mol Life Sci. 2022 Aug 10;79(9):476. doi: 10.1007/s00018-022-04503-y.
Several studies emphasized the function of the thyroid hormones in stem cell biology. These hormones act through the nuclear hormone receptor TRs, which are T3-modulated transcription factors. Pioneer work on T3-dependent amphibian metamorphosis showed that the crosstalk between the epithelium and the underlying mesenchyme is absolutely required for intestinal maturation and stem cell emergence. With the recent advances of powerful animal models and 3D-organoid cultures, similar findings have now begun to be described in mammals, where the action of T3 and TRα1 control physiological and cancer-related stem cell biology. In this review, we have summarized recent findings on the multiple functions of T3 and TRα1 in intestinal epithelium stem cells, cancer stem cells and their niche. In particular, we have highlighted the regulation of metabolic functions directly linked to normal and/or cancer stem cell biology. These findings help explain other possible mechanisms by which TRα1 controls stem cell biology, beyond the more classical Wnt and Notch signaling pathways.
几项研究强调了甲状腺激素在干细胞生物学中的作用。这些激素通过核激素受体 TRs 发挥作用，TRs 是 T3 调节的转录因子。关于 T3 依赖性两栖动物变态的开创性工作表明，上皮细胞和下面的间充质之间的串扰对于肠道成熟和干细胞出现是绝对必需的。随着强大的动物模型和 3D 类器官培养的最新进展，现在在哺乳动物中也开始描述类似的发现，其中 T3 和 TRα1 的作用控制生理和癌症相关的干细胞生物学。在这篇综述中，我们总结了 T3 和 TRα1 在肠道上皮干细胞、癌症干细胞及其龛位中的多种功能的最新发现。特别是，我们强调了与正常和/或癌症干细胞生物学直接相关的代谢功能的调节。这些发现有助于解释 TRα1 控制干细胞生物学的其他可能机制，而不仅仅是更经典的 Wnt 和 Notch 信号通路。
