Whole-Genome Sequencing Identifies Genetic Variances in Culture-Expanded Human Mesenchymal Stem Cells

被引：47

作者：

Cai, Jun ^{[1
]}

Miao, Xuexia ^{[1
,2
]}

Li, Yueying ^{[1
]}

Smith, Cory ^{[3
,4
,5
]}

Tsang, Kitman ^{[4
,5
]}

Cheng, Linzhao ^{[3
,4
,5
]}

Wang, Qian-fei ^{[1
]}

机构：

[1] Chinese Acad Sci, Beijing Inst Genom, Lab Genome Variat & Precis Biomed, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Div Hematol, Baltimore, MD 21205 USA

来源：

STEM CELL REPORTS | 2014年 / 3卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CHROMOSOMAL-ABERRATIONS; CODING MUTATIONS; STROMAL CELLS; ACQUISITION; MOSAICISM; STABILITY; ACCURATE;

D O I：

10.1016/j.stemcr.2014.05.019

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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 (similar to 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.

引用

页码：227 / 233

页数：7

共 33 条

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