Werner Syndrome-specific induced pluripotent stem cells: recovery of telomere function by reprogramming.
Werner Syndrome-specific induced pluripotent stem cells: recovery of telomere function by reprogramming.
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Werner综合征特异性诱导的多能干细胞：通过重编程恢复端粒功能。
DOI：
10.3389/fgene.2015.00010
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发表时间：
2015
影响因子：
3.7
通讯作者：
Tahara H
中科院分区：
文献类型：
--
作者：
Shimamoto A;Yokote K;Tahara H
Werner综合征(WS)是一种罕见的人类常染色体隐性遗传性早衰疾病，以早发衰老相关疾病、染色体不稳定和癌症易感性为特征。WRN编码的DNA解旋酶是WS的致病基因，其功能已被广泛研究。WRN解旋酶通过与DNA修复和端粒维持相关的多种蛋白质相互作用，参与DNA复制、修复和重组，从而维持染色体的完整性。据报道，与WS相关的加速衰老是由端粒功能障碍引起的，其潜在机制尚不清楚。尽管据报道，WS患者的预期寿命在过去20年中有所改善，但对这些患者的明确治疗并没有看到太大的进展。这种疾病的严重症状，如腿部溃疡，会导致WS患者的生活质量显著下降。因此，为该病制定新的治疗策略至关重要。通过将Oct3/4、Sox2、Klf4和c-myc等多潜能基因导入分化细胞，可建立诱导多能干细胞。IPSCs具有分化为构成人体的多种细胞类型的潜力，并具有无限的增殖能力。最近的研究报道了WS患者细胞产生IPSCs，他们得出结论，重新编程可以抑制这些细胞的早衰表型。在本文中，我们总结了WS患者特异性IPSCs(WS IPSCs)的研究结果，并重点介绍了端粒和端粒酶在维持这些细胞中的作用。最后，我们讨论了WS IPSCs在临床上的潜在应用。
Werner syndrome (WS) is a rare human autosomal recessive premature aging disorder characterized by early onset of aging-associated diseases, chromosomal instability, and cancer predisposition. The function of the DNA helicase encoded by WRN, the gene responsible for WS, has been studied extensively. WRN helicase is involved in the maintenance of chromosome integrity through DNA replication, repair, and recombination by interacting with a variety of proteins associated with DNA repair and telomere maintenance. The accelerated aging associated with WS is reportedly caused by telomere dysfunction, and the underlying mechanism of the disease is yet to be elucidated. Although it was reported that the life expectancy for patients with WS has improved over the last two decades, definitive therapy for these patients has not seen much development. Severe symptoms of the disease, such as leg ulcers, cause a significant decline in the quality of life in patients with WS. Therefore, the establishment of new therapeutic strategies for the disease is of utmost importance. Induced pluripotent stem cells (iPSCs) can be established by the introduction of several pluripotency genes, including Oct3/4, Sox2, Klf4, and c-myc into differentiated cells. iPSCs have the potential to differentiate into a variety of cell types that constitute the human body, and possess infinite proliferative capacity. Recent studies have reported the generation of iPSCs from the cells of patients with WS, and they have concluded that reprogramming represses premature senescence phenotypes in these cells. In this review, we summarize the findings of WS patient-specific iPSCs (WS iPSCs) and focus on the roles of telomere and telomerase in the maintenance of these cells. Finally, we discuss the potential use of WS iPSCs for clinical applications.
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影响因子：
64.8
作者：
Batista, Luis F. Z.;Pech, MatthewF.;Zhong, Franklin L.;Nguyen, Ha Nam;Xie, Kathleen T.;Zaug, Arthur J.;Crary, Sharon M.;Choi, Jinkuk;Sebastiano, Vittorio;Cherry, Athena;Giri, Neelam;Wernig, Marius;Alter, Blanche P.;Cech, Thomas R.;Savage, Sharon A.;Pera, Renee A. Reijo;Artandi, Steven E.
通讯作者：
Artandi, Steven E.
影响因子：
3
作者：
Brem, Harold;Lyder, Courtney
通讯作者：
Lyder, Courtney
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Ahn, B;Harrigan, JA;Bohr, VA
通讯作者：
Bohr, VA
DOI：
10.1073/pnas.0609410104
发表时间：
2007-02-13
影响因子：
11.1
作者：
Crabbe, Laure;Jauch, Anna;Karlseder, Jan
通讯作者：
Karlseder, Jan