Comparison of Three Congruent Patient-specific Cell Types for the Modelling of a Human Genetic Schwann-cell Disorder

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2019 Apr 10

PMID 30962586

Citations 19

Authors

Bipasha Mukherjee-Clavin

Ruifa Mi

Barbara Kern

In Young Choi

HoTae Lim

Yohan Oh

Benjamin Lannon

Kevin J Kim

Shaughn Bell

Junho K Hur

Woochang Hwang

Young Hyun Che

Omer Habib

Robert H Baloh

Kevin Eggan

Gerald Brandacher

Ahmet Hoke

Lorenz Studer

Yong Jun Kim

Gabsang Lee

Affiliations

Soon will be listed here.

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.

Citing Articles

From in vivo models to in vitro bioengineered neuromuscular junctions for the study of Charcot-Marie-Tooth disease.

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hESC- and hiPSC-derived Schwann cells are molecularly comparable and functionally equivalent.

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