Whole-genome sequencing identifies genetic variances in culture-expanded human mesenchymal stem cells.
Whole-genome sequencing identifies genetic variances in culture-expanded human mesenchymal stem cells.
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全基因组测序鉴定培养扩增的人类间充质干细胞的遗传变异
DOI：
10.1016/j.stemcr.2014.05.019
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发表时间：
2014-08-12
影响因子：
5.9
通讯作者：
Wang, Qian-fei
中科院分区：
文献类型：
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作者：
Cai, Jun;Miao, Xuexia;Li, Yueying;Smith, Cory;Tsang, Kitman;Cheng, Linzhao;Wang, Qian-fei
培养扩增的人间充质干细胞（MSC）越来越多地用于临床，但缺乏对这些细胞的基因组组成的全面表征。我们提出了一个全基因组研究的遗传动力学培养的骨髓间充质干细胞在离体建立（第1代[p1]）和连续扩增（p8和p13）。我们检测到拷贝数改变（CNA）和低水平的单核苷酸变化（SNCs），直到p8没有显着变化。引人注目的是，在p13 MSC中发现了大量（677）SNCs。使用灵敏的Droplet Digital PCR检测，我们检测了通过全基因组测序检测到的非同义SNCs，发现它们在未培养的单核细胞（约0.01%）和早期传代的MSC（p1和p8时为0.1%-1%）中是预先存在的低频突变，但在p13中达到17%-36%。我们的数据表明，人MSC在离体培养的早期阶段保持稳定的基因组组成，但在延长扩增后进行克隆生长。全基因组研究揭示了培养的MSC沿着连续传代的变化。人MSC在离体培养的早期阶段保持稳定的基因组组成。人MSC在延长的扩增后经历克隆生长。扩增的MSC中存在的“新”SNC预先存在于早期细胞群Wang，Cheng，和同事提出了一个全基因组分析的遗传动力学培养的骨髓间充质干细胞在离体建立（第1代）和连续扩增（第8和13代）。数据表明，人MSC在离体培养的早期阶段保持稳定的基因组组成，但在延长的扩增后经历克隆生长。
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. Whole-genome investigation reveals variances of cultured MSCs along serial passages Human MSCs maintain a stable genomic composition in early stages of ex vivo culture Human MSCs are subject to clonal growth upon extended expansion The “new” SNCs present in the expanded MSCs preexist in the early cell population Wang, Cheng, and colleagues present a whole-genome analysis on genetic dynamics of cultured MSCs under ex vivo establishment (passage 1) and serial expansion (passages 8 and 13). The 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.
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影响因子：
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作者：
Park S;Koh Y;Yoon SS
通讯作者：
Yoon SS
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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影响因子：
7.4
作者：
Hindson, Benjamin J.;Ness, Kevin D.;Masquelier, Donald A.;Belgrader, Phillip;Heredia, Nicholas J.;Makarewicz, Anthony J.;Bright, Isaac J.;Lucero, Michael Y.;Hiddessen, Amy L.;Legler, Tina C.;Kitano, Tyler K.;Hodel, Michael R.;Petersen, Jonathan F.;Wyatt, Paul W.;Steenblock, Erin R.;Shah, Pallavi H.;Bousse, Luc J.;Troup, Camille B.;Mellen, Jeffrey C.;Wittmann, Dean K.;Erndt, Nicholas G.;Cauley, Thomas H.;Koehler, Ryan T.;So, Austin P.;Dube, Simant;Rose, Klint A.;Montesclaros, Luz;Wang, Shenglong;Stumbo, David P.;Hodges, Shawn P.;Romine, Steven;Milanovich, Fred P.;White, Helen E.;Regan, John F.;Karlin-Neumann, George A.;Hindson, Christopher M.;Saxonov, Serge;Colston, Bill W.
通讯作者：
Colston, Bill W.
影响因子：
56.9
作者：
Sjoeblom, Tobias;Jones, Sian;Velculescu, Victor E.
通讯作者：
Velculescu, Victor E.
长期培养的间充质干细胞经常发生基因组突变，但不会发生恶性转化
影响因子：
9
作者：
通讯作者：
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