Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation.
Personal Genome Project Canada
cellular phenotyping
control iPSCs
disease modeling
gene editing
whole-genome sequencing
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
10 12 2019
10 12 2019
Historique:
received:
11
06
2019
revised:
04
11
2019
accepted:
07
11
2019
pubmed:
10
12
2019
medline:
1
7
2020
entrez:
10
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31813827
pii: S2213-6711(19)30406-0
doi: 10.1016/j.stemcr.2019.11.003
pmc: PMC6915802
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1126-1141Subventions
Organisme : NIAID NIH HHS
ID : P01 AI102853
Pays : United States
Organisme : CIHR
ID : THC-135232
Pays : Canada
Organisme : CIHR
ID : SOP-155609
Pays : Canada
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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