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Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder

Patient-specific human induced pluripotent stem cells (hiPSCs) hold great promise for the modelling of genetic disorders. However, these cells display wide intra-individual and inter-individual variations in gene expression, making it challenging to distinguish true-positive and false-positive pheno...

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Autores principales: Mukherjee-Clavin, Bipasha, Mi, Ruifa, Kern, Barbara, Choi, In Young, Lim, Hotae, Oh, Yohan, Lannon, Benjamin, Kim, Kevin J., Bell, Shaughn, Hur, Junho K., Hwang, Woochang, Hyun Che, Young, Habib, Omer, Baloh, Robert H., Eggan, Kevin, Brandacher, Gerald, Hoke, Ahmet, Studer, Lorenz, Jun Kim, Yong, Lee, Gabsang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612317/
https://www.ncbi.nlm.nih.gov/pubmed/30962586
http://dx.doi.org/10.1038/s41551-019-0381-8
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author Mukherjee-Clavin, Bipasha
Mi, Ruifa
Kern, Barbara
Choi, In Young
Lim, Hotae
Oh, Yohan
Lannon, Benjamin
Kim, Kevin J.
Bell, Shaughn
Hur, Junho K.
Hwang, Woochang
Hyun Che, Young
Habib, Omer
Baloh, Robert H.
Eggan, Kevin
Brandacher, Gerald
Hoke, Ahmet
Studer, Lorenz
Jun Kim, Yong
Lee, Gabsang
author_facet Mukherjee-Clavin, Bipasha
Mi, Ruifa
Kern, Barbara
Choi, In Young
Lim, Hotae
Oh, Yohan
Lannon, Benjamin
Kim, Kevin J.
Bell, Shaughn
Hur, Junho K.
Hwang, Woochang
Hyun Che, Young
Habib, Omer
Baloh, Robert H.
Eggan, Kevin
Brandacher, Gerald
Hoke, Ahmet
Studer, Lorenz
Jun Kim, Yong
Lee, Gabsang
author_sort Mukherjee-Clavin, Bipasha
collection PubMed
description Patient-specific human induced pluripotent stem cells (hiPSCs) hold great promise for the modelling of genetic disorders. However, these cells display wide intra-individual and inter-individual variations in gene expression, making it challenging to distinguish true-positive and false-positive phenotypes. Also, data from hiPSC phenotypes and from human embryonic stem cells (hESCs) harbouring the same disease mutation are lacking. Here, we report a comparison of molecular, cellular and functional characteristics of three congruent patient-specific cell types ― hiPSCs, hESCs, and direct lineage-converted cells ― derived from currently available differentiation and direct-reprogramming technologies, for the modelling of Charcot Marie Tooth 1A, a human genetic Schwann-cell disorder featuring a 1.4 megabase chromosomal duplication. In particular, we find that the chemokines CXCL1 and MCP1 are commonly upregulated in all three congruent models and in clinical patient samples. The development of congruent models of a single genetic disease by using somatic cells from a common patient will facilitate the search for convergent phenotypes.
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spelling pubmed-66123172019-10-08 Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder Mukherjee-Clavin, Bipasha Mi, Ruifa Kern, Barbara Choi, In Young Lim, Hotae Oh, Yohan Lannon, Benjamin Kim, Kevin J. Bell, Shaughn Hur, Junho K. Hwang, Woochang Hyun Che, Young Habib, Omer Baloh, Robert H. Eggan, Kevin Brandacher, Gerald Hoke, Ahmet Studer, Lorenz Jun Kim, Yong Lee, Gabsang Nat Biomed Eng Article Patient-specific human induced pluripotent stem cells (hiPSCs) hold great promise for the modelling of genetic disorders. However, these cells display wide intra-individual and inter-individual variations in gene expression, making it challenging to distinguish true-positive and false-positive phenotypes. Also, data from hiPSC phenotypes and from human embryonic stem cells (hESCs) harbouring the same disease mutation are lacking. Here, we report a comparison of molecular, cellular and functional characteristics of three congruent patient-specific cell types ― hiPSCs, hESCs, and direct lineage-converted cells ― derived from currently available differentiation and direct-reprogramming technologies, for the modelling of Charcot Marie Tooth 1A, a human genetic Schwann-cell disorder featuring a 1.4 megabase chromosomal duplication. In particular, we find that the chemokines CXCL1 and MCP1 are commonly upregulated in all three congruent models and in clinical patient samples. The development of congruent models of a single genetic disease by using somatic cells from a common patient will facilitate the search for convergent phenotypes. 2019-04-08 2019-07 /pmc/articles/PMC6612317/ /pubmed/30962586 http://dx.doi.org/10.1038/s41551-019-0381-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Reprints and permissions information is available at www.nature.com/reprints (http://www.nature.com/reprints) .
spellingShingle Article
Mukherjee-Clavin, Bipasha
Mi, Ruifa
Kern, Barbara
Choi, In Young
Lim, Hotae
Oh, Yohan
Lannon, Benjamin
Kim, Kevin J.
Bell, Shaughn
Hur, Junho K.
Hwang, Woochang
Hyun Che, Young
Habib, Omer
Baloh, Robert H.
Eggan, Kevin
Brandacher, Gerald
Hoke, Ahmet
Studer, Lorenz
Jun Kim, Yong
Lee, Gabsang
Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
title Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
title_full Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
title_fullStr Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
title_full_unstemmed Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
title_short Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
title_sort comparison of three congruent patient-specific cell types for the modelling of a human genetic schwann-cell disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612317/
https://www.ncbi.nlm.nih.gov/pubmed/30962586
http://dx.doi.org/10.1038/s41551-019-0381-8
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