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 P...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671119304060 |
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doaj-7ac621f9b435435cbc07d7300e6d6051 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Matthew R. Hildebrandt Miriam S. Reuter Wei Wei Naeimeh Tayebi Jiajie Liu Sazia Sharmin Jaap Mulder L. Stephen Lesperance Patrick M. Brauer Rebecca S.F. Mok Caroline Kinnear Alina Piekna Asli Romm Jennifer Howe Peter Pasceri Guoliang Meng Matthew Rozycki Deivid C. Rodrigues Elisa C. Martinez Michael J. Szego Juan C. Zúñiga-Pflücker Michele K. Anderson Steven A. Prescott Norman D. Rosenblum Binita M. Kamath Seema Mital Stephen W. Scherer James Ellis |
| spellingShingle |
Matthew R. Hildebrandt Miriam S. Reuter Wei Wei Naeimeh Tayebi Jiajie Liu Sazia Sharmin Jaap Mulder L. Stephen Lesperance Patrick M. Brauer Rebecca S.F. Mok Caroline Kinnear Alina Piekna Asli Romm Jennifer Howe Peter Pasceri Guoliang Meng Matthew Rozycki Deivid C. Rodrigues Elisa C. Martinez Michael J. Szego Juan C. Zúñiga-Pflücker Michele K. Anderson Steven A. Prescott Norman D. Rosenblum Binita M. Kamath Seema Mital Stephen W. Scherer James Ellis Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation Stem Cell Reports |
| author_facet |
Matthew R. Hildebrandt Miriam S. Reuter Wei Wei Naeimeh Tayebi Jiajie Liu Sazia Sharmin Jaap Mulder L. Stephen Lesperance Patrick M. Brauer Rebecca S.F. Mok Caroline Kinnear Alina Piekna Asli Romm Jennifer Howe Peter Pasceri Guoliang Meng Matthew Rozycki Deivid C. Rodrigues Elisa C. Martinez Michael J. Szego Juan C. Zúñiga-Pflücker Michele K. Anderson Steven A. Prescott Norman D. Rosenblum Binita M. Kamath Seema Mital Stephen W. Scherer James Ellis |
| author_sort |
Matthew R. Hildebrandt |
| title |
Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation |
| title_short |
Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation |
| title_full |
Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation |
| title_fullStr |
Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation |
| title_full_unstemmed |
Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation |
| title_sort |
precision health resource of control ipsc lines for versatile multilineage differentiation |
| publisher |
Elsevier |
| series |
Stem Cell Reports |
| issn |
2213-6711 |
| publishDate |
2019-12-01 |
| description |
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. : Ellis, Scherer, and colleagues apply precision health to upgrade iPSC quality for disease modeling. The resource provides control lines from four healthy individuals, clinical annotation of whole-genome variants, and identification of variant-preferred lines for neurologic and cardiac disease. Resource users demonstrated versatile differentiation into functional cells from six tissues, and CRISPR-edited cells phenocopied a cardiomyopathy model. Keywords: Personal Genome Project Canada, control iPSCs, whole-genome sequencing, gene editing, cellular phenotyping, disease modeling |
| url |
http://www.sciencedirect.com/science/article/pii/S2213671119304060 |
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doaj-7ac621f9b435435cbc07d7300e6d60512020-11-25T01:38:39ZengElsevierStem Cell Reports2213-67112019-12-0113611261141Precision Health Resource of Control iPSC Lines for Versatile Multilineage DifferentiationMatthew R. Hildebrandt0Miriam S. Reuter1Wei Wei2Naeimeh Tayebi3Jiajie Liu4Sazia Sharmin5Jaap Mulder6L. Stephen Lesperance7Patrick M. Brauer8Rebecca S.F. Mok9Caroline Kinnear10Alina Piekna11Asli Romm12Jennifer Howe13Peter Pasceri14Guoliang Meng15Matthew Rozycki16Deivid C. Rodrigues17Elisa C. Martinez18Michael J. Szego19Juan C. Zúñiga-Pflücker20Michele K. Anderson21Steven A. Prescott22Norman D. Rosenblum23Binita M. Kamath24Seema Mital25Stephen W. Scherer26James Ellis27Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaNeurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDepartment of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, CanadaGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDepartment of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaDalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, ON M5C 2T2, Canada; The Joint Centre for Bioethics, University of Toronto, Toronto, ON, Canada; Unity Health Toronto, Toronto, ON M5T 3M6, CanadaDepartment of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaDepartment of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON M4N 3M5, CanadaNeurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, CanadaDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, CanadaGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, CanadaGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; McLaughlin Centre, University of Toronto, Toronto, ON M5G 0A4, Canada; Corresponding authorDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Corresponding authorSummary: 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. : Ellis, Scherer, and colleagues apply precision health to upgrade iPSC quality for disease modeling. The resource provides control lines from four healthy individuals, clinical annotation of whole-genome variants, and identification of variant-preferred lines for neurologic and cardiac disease. Resource users demonstrated versatile differentiation into functional cells from six tissues, and CRISPR-edited cells phenocopied a cardiomyopathy model. Keywords: Personal Genome Project Canada, control iPSCs, whole-genome sequencing, gene editing, cellular phenotyping, disease modelinghttp://www.sciencedirect.com/science/article/pii/S2213671119304060 |