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 language | English (US) |
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Pages (from-to) | 227-233 |
Number of pages | 7 |
Journal | Stem Cell Reports |
Volume | 3 |
Issue number | 2 |
DOIs | |
State | Published - Aug 12 2014 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Genetics
- Developmental Biology
- Cell Biology