Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder.
Nat Biomed Eng
; 3(7): 571-582, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30962586
ABSTRACT
Patient-specific human-induced pluripotent stem cells (hiPSCs) hold great promise for the modelling of genetic disorders. However, these cells display wide intra- and interindividual variations in gene expression, which makes distinguishing true-positive and false-positive phenotypes challenging. Data from hiPSC phenotypes and human embryonic stem cells (hESCs) harbouring the same disease mutation are also lacking. Here, we report a comparison of the 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 use in the modelling of Charcot-Marie-Tooth 1A, a human genetic Schwann-cell disorder featuring a 1.4 Mb chromosomal duplication. We find that the chemokines C-X-C motif ligand chemokine-1 (CXCL1) and macrophage chemoattractant protein-1 (MCP1) are commonly upregulated in all three congruent models and in clinical patient samples. The development of congruent models of a single genetic disease using somatic cells from a common patient will facilitate the search for convergent phenotypes.
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Base de dados:
MEDLINE
Assunto principal:
Células de Schwann
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Quimiocina CCL2
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Quimiocina CXCL1
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Células-Tronco Pluripotentes Induzidas
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Doenças Genéticas Inatas
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article