Stem cell development involves divergent thyroid hormone receptor subtype expression and epigenetic modifications in the Xenopus metamorphosing intestine
Stem cell development involves divergent thyroid hormone receptor subtype expression and epigenetic modifications in the Xenopus metamorphosing intestine
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DOI：
10.1016/j.ygcen.2020.113441
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发表时间：
2020-06-01
影响因子：
2.7
通讯作者：
Ishizuya-Oka, Atsuko
中科院分区：
文献类型：
--
作者：
Hasebe, Takashi;Fujimoto, Kenta;Ishizuya-Oka, Atsuko
在青蛙爪蟾变态期间的肠中，大多数幼虫上皮细胞被甲状腺激素（TH）诱导经历凋亡，并且在持续的TH作用下，剩余的上皮细胞去分化为干细胞（SC），然后新产生类似于哺乳动物肠上皮的成体上皮。以前，我们已经表明，存在于幼虫上皮分化的吸收细胞的SC的前体特异性表达受体酪氨酸激酶样孤儿受体2（Ror 2）。通过使用Ror 2作为标记物，我们已经在此用化学方法表明，这些SC前体细胞表达TH受体α（TR α），而不是注定因凋亡而死亡的幼虫上皮细胞。在TH依赖性重塑开始后，TR α表达仍然限于SC以及源自SC的增殖的成体上皮原基。随着肠皱襞的形成，TR α表达定位于SC所在的皱襞的波谷。相反，TA β表达在整个肠道中瞬时上调，伴随着内源性TH水平的增加，并且在发育中的成体上皮原基中表达最高。此外，我们在这里已经表明，全球组蛋白H4乙酰化增强的SC前体和成人原基，包括SC，而三甲基化的组蛋白H3赖氨酸27是缺乏在这些细胞在变态。我们的研究结果强烈表明TR α和TA β在肠道幼虫到成人重塑中的不同作用，涉及SC谱系中独特的表观遗传修饰。
In the intestine during metamorphosis of the frog Xenopus laevis, most of the larval epithelial cells are induced to undergo apoptosis by thyroid hormone (TH), and under continued TH action, the remaining epithelial cells dedifferentiate into stem cells (SCs), which then newly generate an adult epithelium analogous to the mammalian intestinal epithelium. Previously, we have shown that the precursors of the SCs that exist in the larval epithelium as differentiated absorptive cells specifically express receptor tyrosine kinase-like orphan receptor 2 (Ror2). By using Ror2 as a marker, we have immunohistochemically shown here that these SC precursors, but not the larval epithelial cells destined to die by apoptosis, express TH receptor alpha (TR alpha). Upon initiation of TH-dependent remodeling, TR alpha expression remains restricted to the SCs as well as proliferating adult epithelial primordia derived from them. As intestinal folds form, TR alpha expression becomes localized in the trough of the folds where the SCs reside. In contrast, TA beta expression is transiently up-regulated in the entire intestine concomitantly with the increase of endogenous TH levels and is most highly expressed in the developing adult epithelial primordia. Moreover, we have shown here that global histone H4 acetylation is enhanced in the SC precursors and adult primordia including the SCs, while tri-methylation of histone H3 lysine 27 is lacking in those cells during metamorphosis. Our results strongly suggest distinct roles of TR alpha and TA beta in the intestinal larval-to-adult remodeling, involving distinctive epigenetic modifications in the SC lineage.