Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome
Xonia Carvajal-Vergara,Ana Sevilla,Sunita L. D’Souza,Yen-Sin Ang,Christoph Schaniel,Dung Fang Lee,Lei Yang,Aaron D. Kaplan,Eric Adler,Roye Rozov,Yongchao Ge,Ninette Cohen,Lisa Edelmann,Betty Chang,Avinash Waghray,Jie Su,Sherly Pardo,Klaske D. Lichtenbelt,Marco Tartaglia,Bruce D. Gelb,Ihor R. Lemischka +20 more
TLDR
In vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomeocytes derived from human embryonic stem cells or wild-type iPSC derived from a healthy brother of one of the LEopARD syndrome patients, which correlate with a potential hypertrophic state.Abstract:
The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems. The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.read more
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Induced pluripotency: history, mechanisms, and applications
TL;DR: This review summarizes the progress that has been made in the iPSC field over the last 4 years, with an emphasis on understanding the mechanisms of cellular reprogramming and its potential applications in cell therapy.
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Engineering Adolescence Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes
TL;DR: Progress in promoting the maturation of the hPSC cardiomyocytes is discussed, in the context of the current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes.
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Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes
Sara S. Nunes,Jason W. Miklas,Jie Liu,Roozbeh Aschar-Sobbi,Yun Xiao,Boyang Zhang,Jiahua Jiang,Stéphane Massé,Mark Gagliardi,Anne Hsieh,Nimalan Thavandiran,Michael A. Laflamme,Kumaraswamy Nanthakumar,Gil J. Gross,Peter H. Backx,Peter H. Backx,Gordon Keller,Milica Radisic +17 more
TL;DR: It is demonstrated that the engineered platform allows for the generation of three-dimensional, aligned cardiac tissues (biowires) with frequent striations and that the responses of immature human myocardium to electrical stimulation and pacing are in agreement with cardiomyocyte maturation.
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Pluripotency and Cellular Reprogramming: Facts, Hypotheses, Unresolved Issues
TL;DR: Recent advances in in-vitro reprogramming of somatic cells to induced pluripotent stem cells are reviewed and unresolved and controversial questions are emphasized.
Journal ArticleDOI
High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents
Junyi Ma,Liang Guo,Steve Fiene,Blake D. Anson,James A. Thomson,Timothy J. Kamp,Kyle L. Kolaja,Bradley J. Swanson,Craig T. January +8 more
TL;DR: Detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes concludes that they have ionic currents and channel gating properties underlying their APs and EADs that are quantitatively similar to those reported for human cardiac myocytes.
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Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons.
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TL;DR: Induced pluripotent stem cells are generated from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.
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Induced pluripotent stem cells from a spinal muscular atrophy patient
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