Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation
Summary
Induced pluripotent stem cells (iPSC) derived from healthy individuals are important controls for disease-modeling studies. Here we apply precision health to create a high-quality resource of control iPSCs. Footprint-free lines were reprogrammed from four volunteers of the Personal Genome Project Canada (PGPC). Multilineage-directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users demonstrated versatility by generating kidney organoids, T lymphocytes, and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited the expected hypertrophic phenotype. Whole-genome sequencing-based annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harbored at least one pre-existing or acquired variant with cardiac, neurological, or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cells from six tissues for disease modeling, and variant-preferred healthy control lines were identified for specific disease settings. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Hildebrandt MR, Reuter MS, Wei W, Tayebi N, Liu J, Sharmin S, Mulder J, Lesperance LS, Brauer PM, Mok RSF, Kinnear C, Piekna A, Romm A, Howe J, Pasceri P, Meng G, Rozycki M, Rodrigues DC, Martinez EC, Szego MJ, Zúñiga-Pflücker JC, Anderson MK, Prescott SA, Rosenblum ND, Kamath BM, Mital S, Scherer SW, Ellis J |
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| Journal | Stem cell reports |
| Publication Date | 2019 Dec 10;13(6):1126-1141 |
| PubMed | 31813827 |
| PubMed Central | PMC6915802 |
| DOI | 10.1016/j.stemcr.2019.11.003 |