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 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.