Mukherjee-Clavin B, Mi R, Kern B, Choi IY, Lim H, Oh Y, Lannon B, Kim KJ, Bell S, Hur JK, Hwang W, Che YH, Habib O, Baloh RH, Eggan K, Brandacher G, Hoke A, Studer L, Kim YJ, Lee G. 2019. Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder. Nature biomedical engineering. 3(7):571-582. Pubmed: 30962586 DOI:10.1038/s41551-019-0381-8


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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Kevin Eggan investigates the mechanisms that cause motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS), and seeks to translate new discoveries into new therapeutic options for patients.

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