An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development.
An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development.
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DOI：
10.1002/stem.529
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发表时间：
2010-11
期刊：
影响因子：
5.2
通讯作者：
Shi, Yun-Bo
中科院分区：
文献类型：
--
作者：
Matsuda, Hiroki;Shi, Yun-Bo
关键词：
器官特异性成体干细胞对成体器官的稳态和器官修复再生至关重要。不幸的是，研究这些干细胞的起源及其发育机制一直很困难，特别是在哺乳动物中。青蛙蜕变过程中的肠道重塑为这类研究提供了独特的机会。在从食草蝌蚪到食肉青蛙的转变过程中，肠道被完全重塑，幼虫上皮细胞发生凋亡变性，并被新生的成体上皮细胞所取代。整个变质过程受甲状腺激素的控制，使控制成体肠道干细胞的发育成为可能。我们在这里表明，甲状腺激素受体共激活因子PRMT1（蛋白精氨酸甲基转移酶1）在少数幼虫上皮细胞中上调，这些细胞去分化成为成体干细胞。更重要的是，转基因PRMT1的过表达导致肠内成体干细胞增加，反之，敲低内源性PRMT1的表达会减少成体干细胞。此外，斑马鱼和小鼠发育过程中PRMT1的表达模式表明，PRMT1在整个脊椎动物成体肠道干细胞的发育中起着进化保守的作用。这些发现不仅对了解器官特异性成体干细胞的发育具有重要意义，而且对消化道再生医学也具有重要意义。
Organ-specific adult stem cells are critical for the homeostasis of adult organs and organ repair and regeneration. Unfortunately, it has been difficult to investigate the origins of these stem cells and the mechanisms of their development, especially in mammals. Intestinal remodeling during frog metamorphosis offers a unique opportunity for such studies. During the transition from an herbivorous tadpole to a carnivorous frog, the intestine is completely remodeled with the larval epithelial cells undergo apoptotic degeneration and are replaced by adult epithelial cells developed de novo. The entire metamorphic process is under the control of thyroid hormone, making it possible to control the development of the adult intestinal stem cells. We show here that the thyroid hormone receptor-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, transgenic overexpression of PRMT1 leads to increase adult stem cells in the intestine and conversely knocking down the expression of endogenous PRMT1 reduces the adult stem cells. In addition, PRMT1 expression pattern during zebrafish and mouse development suggests that PRMT1 plays an evolutionally conserved role in the development of adult intestinal stem cells throughout vertebrates. 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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