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

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.

SUBMITTER: Cai J 

PROVIDER: S-EPMC4176531 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Cai Jun J   Miao Xuexia X   Li Yueying Y   Smith Cory C   Tsang Kitman K   Cheng Linzhao L   Wang Qian-Fei QF  

Stem cell reports 20140626 2

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  ...[more]

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