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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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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. |
format | Online Article Text |
id | pubmed-6612317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
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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