Tissue-specific upregulation of MDS/EVI gene transcripts in the intestine by thyroid hormone during Xenopus metamorphosis.

Tissue-specific upregulation of MDS/EVI gene transcripts in the intestine by thyroid hormone during Xenopus metamorphosis.
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DOI:
10.1371/journal.pone.0055585
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Shi YB
Shi YB
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miller TC;Sun G;Hasebe T;Fu L;Heimeier RA;Das B;Ishizuya-Oka A;Shi YB

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两栖动物变态过程中的肠重塑类似于哺乳动物胚后发育过程中成体肠的成熟,此时成体上皮自我更新系统在高浓度血浆甲状腺激素(T3)的影响下建立。该过程涉及成体干细胞的从头形成和随后的增殖和分化。非洲爪蟾变态过程中成体肠干细胞形成的T3依赖性提供了一个独特的机会,以确定可能对成体器官特异性干细胞发育重要的基因。我们已经克隆并表征了异位病毒整合位点1(EVI)及其变体骨髓增生异常综合征1(MDS)/EVI,其通过从上游MDS启动子转录和选择性剪接产生。EVI和MDS/EVI与许多癌症有关,包括乳腺癌、白血病、卵巢癌和肠癌。我们发现,EVI和MDS/EVI转录上调T3在上皮细胞,但不是非洲爪蟾肠的其余部分时,成人干细胞形成的上皮。我们的研究结果表明,EVI和MDS/EVI可能参与新形成的成人肠上皮细胞的发育和/或增殖。
Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells. The T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium. Our results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells.
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