Whole-genome sequencing identifies genetic variances in culture-expanded human mesenchymal stem cells

Jun Cai, Xuexia Miao, Yueying Li, Cory Smith, Kitman Tsang, Linzhao Cheng, Qian Fei Wang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Culture-expanded human mesenchymal stem cells (MSCs) are increasingly used in clinics, yet full characterization of the genomic compositions of these cells is lacking. We present a whole-genome investigation on the genetic dynamics of cultured MSCs under ex vivo establishment (passage 1 [p1]) and serial expansion (p8 and p13). We detected no significant changes in copy-number alterations (CNAs) and low levels of single-nucleotide changes (SNCs) until p8. Strikingly, a significant number (677) of SNCs were found in p13 MSCs. Using a sensitive Droplet Digital PCR assay, we tested the nonsynonymous SNCs detected by whole-genome sequencing and found that they were preexisting low-frequency mutations in uncultured mononuclear cells (∼0.01%) and early-passage MSCs (0.1%-1% at p1 and p8) but reached 17%-36% in p13. Our data demonstrate that human MSCs maintain a stable genomic composition in the early stages of ex vivo culture but are subject to clonal growth upon extended expansion.

Original languageEnglish (US)
Pages (from-to)227-233
Number of pages7
JournalStem Cell Reports
Volume3
Issue number2
DOIs
StatePublished - Aug 12 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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