PMID- 30962586 OWN - NLM STAT- MEDLINE DCOM- 20200309 LR - 20210113 IS - 2157-846X (Electronic) IS - 2157-846X (Linking) VI - 3 IP - 7 DP - 2019 Jul TI - Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder. PG - 571-582 LID - 10.1038/s41551-019-0381-8 [doi] AB - 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. FAU - Mukherjee-Clavin, Bipasha AU - Mukherjee-Clavin B AD - Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Mi, Ruifa AU - Mi R AD - Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Kern, Barbara AU - Kern B AD - Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Surgery, Charite-Universitatsmedizin, Berlin, Germany. FAU - Choi, In Young AU - Choi IY AD - Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Lim, Hotae AU - Lim H AD - Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Oh, Yohan AU - Oh Y AUID- ORCID: 0000-0002-9249-8664 AD - Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Medicine, College of Medicine, Hanyang University, Seoul, South Korea. FAU - Lannon, Benjamin AU - Lannon B AUID- ORCID: 0000-0003-1082-0910 AD - Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. AD - Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA. AD - Boston IVF, Waltham, MA, USA. FAU - Kim, Kevin J AU - Kim KJ AD - Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA. FAU - Bell, Shaughn AU - Bell S AD - Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA. FAU - Hur, Junho K AU - Hur JK AD - Department of Pathology, College of Medicine, Kyung Hee University, Seoul, South Korea. AD - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea. FAU - Hwang, Woochang AU - Hwang W AD - Data Science for Knowledge Creation Research Centre, Seoul National University, Seoul, South Korea. FAU - Che, Young Hyun AU - Che YH AD - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea. FAU - Habib, Omer AU - Habib O AD - Department of Pathology, College of Medicine, Kyung Hee University, Seoul, South Korea. FAU - Baloh, Robert H AU - Baloh RH AD - Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA. AD - Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. FAU - Eggan, Kevin AU - Eggan K AUID- ORCID: 0000-0003-4436-8467 AD - Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. FAU - Brandacher, Gerald AU - Brandacher G AD - Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Hoke, Ahmet AU - Hoke A AUID- ORCID: 0000-0003-1215-3373 AD - Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Studer, Lorenz AU - Studer L AUID- ORCID: 0000-0003-0741-7987 AD - Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA. FAU - Kim, Yong Jun AU - Kim YJ AUID- ORCID: 0000-0002-5374-712X AD - Department of Pathology, College of Medicine, Kyung Hee University, Seoul, South Korea. yjkim1@khu.ac.kr. AD - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea. yjkim1@khu.ac.kr. FAU - Lee, Gabsang AU - Lee G AUID- ORCID: 0000-0002-5052-5927 AD - Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. glee48@jhmi.edu. AD - Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. glee48@jhmi.edu. AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. glee48@jhmi.edu. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R01 AR070751/AR/NIAMS NIH HHS/United States GR - R01 NS093213/NS/NINDS NIH HHS/United States GR - R01 NS097545/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190408 PL - England TA - Nat Biomed Eng JT - Nature biomedical engineering JID - 101696896 RN - 0 (CCL2 protein, human) RN - 0 (CXCL1 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL1) RN - 0 (Chemokines) RN - 0 (Myelin Proteins) RN - 0 (Octamer Transcription Factor-3) RN - 0 (PMP22 protein, human) RN - 0 (POU5F1 protein, human) RN - 0 (SOX10 protein, human) RN - 0 (SOXE Transcription Factors) SB - IM MH - Adult MH - Animals MH - CRISPR-Cas Systems MH - Cell Differentiation/genetics MH - Cell Line MH - Cell Lineage/genetics MH - Cells, Cultured MH - Cellular Reprogramming MH - Chemokine CCL2/*genetics/metabolism MH - Chemokine CXCL1/*genetics/metabolism MH - Chemokines MH - Embryonic Stem Cells/pathology MH - Female MH - Gene Editing MH - Gene Expression MH - Gene Expression Profiling MH - *Genetic Diseases, Inborn MH - Genetic Predisposition to Disease/genetics MH - Human Genetics MH - Humans MH - Induced Pluripotent Stem Cells/*metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred NOD MH - Myelin Proteins/genetics/metabolism MH - Octamer Transcription Factor-3/genetics/metabolism MH - Phenotype MH - Rats MH - SOXE Transcription Factors/genetics/metabolism MH - Schwann Cells/*metabolism/pathology MH - Transplantation PMC - PMC6612317 MID - NIHMS1523235 COIS- Competing interests The authors declare no competing interests. EDAT- 2019/04/10 06:00 MHDA- 2020/03/10 06:00 PMCR- 2019/10/08 CRDT- 2019/04/10 06:00 PHST- 2017/07/17 00:00 [received] PHST- 2019/03/05 00:00 [accepted] PHST- 2019/04/10 06:00 [pubmed] PHST- 2020/03/10 06:00 [medline] PHST- 2019/04/10 06:00 [entrez] PHST- 2019/10/08 00:00 [pmc-release] AID - 10.1038/s41551-019-0381-8 [pii] AID - 10.1038/s41551-019-0381-8 [doi] PST - ppublish SO - Nat Biomed Eng. 2019 Jul;3(7):571-582. doi: 10.1038/s41551-019-0381-8. Epub 2019 Apr 8.