1. Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
- Author
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Hotae Lim, Shaughn Bell, Kevin Eggan, B.M. Lannon, Young Hyun Che, Barbara Kern, Gabsang Lee, Woochang Hwang, Yohan Oh, Bipasha Mukherjee-Clavin, Junho K. Hur, Omer Habib, Ahmet Hoke, Gerald Brandacher, Ruifa Mi, Kevin J. Kim, Lorenz Studer, Robert H. Baloh, In Young Choi, and Yong Jun Kim
- Subjects
Male ,0301 basic medicine ,Somatic cell ,Chemokine CXCL1 ,Gene Expression ,Medicine (miscellaneous) ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,Gene duplication ,Induced pluripotent stem cell ,Cells, Cultured ,Chemokine CCL2 ,Gene Editing ,SOXE Transcription Factors ,Cell Differentiation ,Cellular Reprogramming ,3. Good health ,Computer Science Applications ,Phenotype ,Female ,Chemokines ,Myelin Proteins ,Biotechnology ,Adult ,Cell type ,Induced Pluripotent Stem Cells ,Biomedical Engineering ,Bioengineering ,Computational biology ,Biology ,Article ,Cell Line ,03 medical and health sciences ,Animals ,Humans ,Cell Lineage ,Genetic Predisposition to Disease ,Embryonic Stem Cells ,Transplantation ,Gene Expression Profiling ,Genetic Diseases, Inborn ,Human Genetics ,Embryonic stem cell ,Human genetics ,Rats ,Gene expression profiling ,030104 developmental biology ,Schwann Cells ,CRISPR-Cas Systems ,Octamer Transcription Factor-3 ,030217 neurology & neurosurgery - 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. A comparison of the molecular, cellular and functional characteristics of three congruent patient-specific cell types for the modelling of Charcot−Marie−Tooth 1A reveals commonly upregulated chemokines.
- Published
- 2019
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