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| Status |
Public on May 22, 2019 |
| Title |
Modeling CMT1A with human induced pluripotent stem cell derived Schwann cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
We obtained skin fibroblasts from CMT1A and control patients, and generated hiPSCs which were subsequently differentiated into cd49d+ human Schwann cells. We utilized microarray technology to explore the gene expression profiles of cd49d+ Schwann cells CMT1A hiPSCs, control hiPSCs, and control human embryonic stem cells in order to identify potentially disregulated pathways contributing to CMT1A pathogenesis.
Patient-specific human induced pluripotent stem cells (hiPSCs) hold great promise for disease modeling of genetic disorders. Often the findings from hiPSC-based studies are validated with genetically-corrected hiPSCs generated by precise genome editing technologies, however, alternatives that have not yet been employed are validation with embryonic stem cells harboring the same disease mutation or utilizing another reprogramming approach from somatic cells of same patients. Here we report that disease-relevant phenotypes found in Charcot-Marie-Tooth 1A (CMT1A)-hiPSC-derived Schwann cells were further confirmed by two additional congruent CMT1A models as an alternative to gene correction. We have devised a defined and relatively fast protocol for the direct derivation and prospective isolation of Schwann cells from hiPSCs, leading us to uncover a phenotype of dysregulated immune signaling in CMT1A-hiPSCs-Schwann cells. Our study illustrates the promise of applying hiPSC technology to one of the most common hereditary neuropathies for gaining new insights into human disease pathogenesis and treatment, and these results demonstrate the feasibility of verifying disease phenotypes by utilizing the malleability of cellular fates.
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| Overall design |
hiPSC-Schwann cells from one CMT1A patient (3 samples), an unrelated patient (1 sample), a control hiPSC line (2 samples) and a control hESC line (2 samples) were analyzed using the Affy Primeview array
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| Contributor(s) |
Mukherjee-Clavin B, Lee G |
| Citation(s) |
30962586 |
| Submission date |
Jun 18, 2015 |
| Last update date |
Aug 21, 2019 |
| Contact name |
Gabsang Lee |
| E-mail(s) |
glee48@jhmi.edu
|
| Phone |
443-287-8631
|
| Organization name |
The Johns Hopkins University
|
| Department |
School of Medicine
|
| Lab |
Institute for Cell Engineering
|
| Street address |
733 North Broadway
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
|
| Samples (8)
|
| GSM1715401 |
CMT1A hiPSC 5148 Schwann cells - biological repeat 1 |
| GSM1715402 |
CMT1A hiPSC 5148 Schwann cells - biological repeat 2 |
| GSM1715403 |
CMT1A hiPSC 5148 Schwann cells - biological repeat 3 |
| GSM1715404 |
CMT1A hiPSC 5165 Schwann cells - biological repeat 1 |
| GSM1715405 |
Control hiPSC 2623 Schwann cells - biological repeat 1 |
| GSM1715406 |
Control hiPSC 2623 Schwann cells - biological repeat 2 |
| GSM1715407 |
Control hESC H9 Schwann cells - biological repeat 1 |
| GSM1715408 |
Control hESC H9 Schwann cells - biological repeat 2 |
|
| Relations |
| BioProject |
PRJNA287351 |
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