Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation

Stem Cell Reports. 2019 Dec 10;13(6):1126-1141. doi: 10.1016/j.stemcr.2019.11.003.

Abstract

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.

Keywords: Personal Genome Project Canada; cellular phenotyping; control iPSCs; disease modeling; gene editing; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Cell Differentiation*
  • Cell Lineage*
  • Cell Self Renewal
  • Cell Separation
  • Ectoderm / cytology
  • Ectoderm / metabolism
  • Gene Editing
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Organoids
  • Phenotype
  • T-Lymphocytes / metabolism
  • Whole Genome Sequencing