Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1~(MET)

Shalom-Feuerstein R.; Serror L.; Aberdam E.Müller F.-J.Van Bokhoven H.Wiman K.G.Zhou H.Aberdam D.Petit I.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1~(MET)

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Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1~(MET)

机译：Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1~(MET)

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Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellularmodel that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stemcell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18~+ cells but failed to further differentiate into K14~+ cells (epidermis/limbus) or K3/K12~+ cells (corneal epithelium). APR-246 (PRIMA-1 ~(MET)), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate a normal p63-related signaling pathway. This study illustrates the relevance of iPSC for p63 related disorders and paves theway for future therapy of EEC.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第6期|2152-2156|共5页
作者
Shalom-Feuerstein R.; Serror L.; Aberdam E.Müller F.-J.Van Bokhoven H.Wiman K.G.Zhou H.Aberdam D.Petit I.;
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作者单位

Institut National de la Santé et de la Recherche Médicale U898, University of Nice, 06107 Nice, France;

Bruce Rappaport Faculty of Medicine, Stem Cell Research Center, INSERTECH, Haifa 31096, Israel;

Zentrum für Integrative Psychiatrie, 24105 Kiel, GermanyDepartment of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centrum, 6500 HB, Nijmegen, NetherlandsDepartment of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cornea; Rare disease; TRP63;

Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1~(MET)

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