A library of induced pluripotent stem cells from clinically well-characterized, diverse healthy human individuals

Stem Cell Reports. 2021 Dec 14;16(12):3036-3049. doi: 10.1016/j.stemcr.2021.10.005. Epub 2021 Nov 4.

Abstract

A library of well-characterized human induced pluripotent stem cell (hiPSC) lines from clinically healthy human subjects could serve as a useful resource of normal controls for in vitro human development, disease modeling, genotype-phenotype association studies, and drug response evaluation. We report generation and extensive characterization of a gender-balanced, racially/ethnically diverse library of hiPSC lines from 40 clinically healthy human individuals who range in age from 22 to 61 years. The hiPSCs match the karyotype and short tandem repeat identities of their parental fibroblasts, and have a transcription profile characteristic of pluripotent stem cells. We provide whole-genome sequencing data for one hiPSC clone from each individual, genomic ancestry determination, and analysis of mendelian disease genes and risks. We document similar transcriptomic profiles, single-cell RNA-sequencing-derived cell clusters, and physiology of cardiomyocytes differentiated from multiple independent hiPSC lines. This extensive characterization makes this hiPSC library a valuable resource for many studies on human biology.

Keywords: age- and sex-independent gene signature; cardiomyocytes; clinically well-characterized healthy subjects; genetic variants of mild common disease phenotypes or more severe disease with incomplete penetrance; induced pluripotent stem cells; racially/ethnically diverse; similar physiology and transcriptomes; whole-genome sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcium Signaling
  • Cell Differentiation
  • Cell Line
  • Clone Cells
  • Ethnicity
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Health*
  • Heart Atria / cytology
  • Heart Ventricles / cytology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Male
  • Middle Aged
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Risk Factors
  • Young Adult