Dynamic Features of Chromosomal Instability during Culture of Induced Pluripotent Stem Cells.
Dynamic Features of Chromosomal Instability during Culture of Induced Pluripotent Stem Cells.
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作者：
诱导多能干细胞(IPSCs)在再生医学中具有巨大的潜力。通过对患者自身细胞进行重新编程，可以在移植过程中避免免疫排斥。为了扩增和基因编辑，iPSCs在人工培养中生长了很长时间。文化为遗传变异的积累提供了潜在的危险。为了研究这些问题，我们培养了两个诱导多能干细胞(IPS)细胞系，并使用先进的光学图谱对其进行周期性分析，以检测和分类染色体的数目和节段性变化，包括缺失、插入、平衡易位和倒置。在其中一个品系中，12号染色体的三体群体在少数传代中获得了优势。通过染色体铺展分析，通过中间传代追踪了12号染色体三体细胞培养的这种外观和显性。数学模型表明，二倍体细胞对三体细胞的增殖率不能解释三体群体的快速优势。此外，光学测绘揭示了数百种结构变异，与通常在人类群体中发现的那些不同。其中许多结构变异是在培养过程早期获得的样本中检测到的，并在传代后期的样本中保持不变，而另一些结构变异是在培养过程中获得的。
Induced pluripotent stem cells (iPSCs) hold great potential for regenerative medicine. By reprogramming a patient′s own cells, immunological rejection can be avoided during transplantation. For expansion and gene editing, iPSCs are grown in artificial culture for extended times. Culture affords potential danger for the accumulation of genetic aberrations. To study these, two induced pluripotent stem (iPS) cell lines were cultured and periodically analyzed using advanced optical mapping to detect and classify chromosome numerical and segmental changes that included deletions, insertions, balanced translocations and inversions. In one of the lines, a population trisomic for chromosome 12 gained dominance over a small number of passages. This appearance and dominance of the culture by chromosome 12 trisomic cells was tracked through intermediate passages by the analysis of chromosome spreads. Mathematical modeling suggested that the proliferation rates of diploid versus trisomic cells could not account for the rapid dominance of the trisomic population. In addition, optical mapping revealed hundreds of structural variations distinct from those generally found within the human population. Many of these structural variants were detected in samples obtained early in the culturing process and were maintained in late passage samples, while others were acquired over the course of culturing.
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影响因子：
5.9
作者：
Baker, Duncan;Hirst, Adam J.;Gokhale, Paul J.;Juarez, Miguel A.;Williams, Steve;Wheeler, Mark;Bean, Kerry;Allison, Thomas F.;Moore, Harry D.;Andrews, Peter W.;Barbaric, Ivana
通讯作者：
Barbaric, Ivana
影响因子：
3.7
作者：
Akutsu SN;Miyamoto T;Oba D;Tomioka K;Ochiai H;Ohashi H;Matsuura S
通讯作者：
Matsuura S
影响因子：
64.8
作者：
Kilpinen H;Goncalves A;Leha A;Afzal V;Alasoo K;Ashford S;Bala S;Bensaddek D;Casale FP;Culley OJ;Danecek P;Faulconbridge A;Harrison PW;Kathuria A;McCarthy D;McCarthy SA;Meleckyte R;Memari Y;Moens N;Soares F;Mann A;Streeter I;Agu CA;Alderton A;Nelson R;Harper S;Patel M;White A;Patel SR;Clarke L;Halai R;Kirton CM;Kolb-Kokocinski A;Beales P;Birney E;Danovi D;Lamond AI;Ouwehand WH;Vallier L;Watt FM;Durbin R;Stegle O;Gaffney DJ
通讯作者：
Gaffney DJ
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
影响因子：
3.5
作者：
Grassmann, Felix;Friedrich, Ulrike;Fauser, Sascha;Schick, Tina;Milenkovic, Andrea;Schulz, Heidi L.;von Strachwitz, Claudia N.;Bettecken, Thomas;Lichtner, Peter;Meitinger, Thomas;Arend, Nicole;Wolf, Armin;Haritoglou, Christos;Rudolph, Guenther;Chakravarthy, Usha;Silvestri, Giuliana;McKay, Gareth J.;Freitag-Wolf, Sandra;Krawczak, Michael;Smith, R. Theodore;Merriam, John C.;Merriam, Joanna E.;Allikmets, Rando;Heid, Iris M.;Weber, Bernhard H. F.
通讯作者：
Weber, Bernhard H. F.