Cell Stem Cell：ips细胞具更高基因畸变频率 * m0 Z, E% E9 D' ^8 P/ V2 U: H& l$ J9 c U, y1 Q/ y6 J2 V
Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and iPSCs during Reprogramming and Time in Culture , A; g0 a% J7 m7 m! Z2 B / b! _ ~7 I' [5 G* I7 u/ j) ACell Stem Cell, Volume 8, Issue 1, 106-118, 7 January 20115 s n$ L( O7 e0 x
Copyright 2011 Elsevier Inc. All rights reserved. 9 W7 [6 P- \# i+ V. q10.1016/j.stem.2010.12.003- Z/ z7 U* M+ ]- [+ T5 e
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Louise C. Laurent, Igor Ulitsky, Ileana Slavin, Ha Tran, Andrew Schork, Robert Morey, Candace Lynch, Julie V. Harness, Sunray Lee, Maria J. Barrero, Sherman Ku, Marina Martynova, Ruslan Semechkin, Vasiliy Galat, Joel Gottesfeld, Juan Carlos Izpisua Belmonte, Chuck Murry, Hans S. Keirstead, Hyun-Sook Park, Uli Schmidt, Andrew L. Laslett, Franz-Josef Muller, Caroline M. Nievergelt, Ron Shamir, Jeanne F. Loring' |5 c h3 y9 C0 g: A
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Highlights - ` G& V k7 \/ D•hESCs and hiPSCs show more gene copy number variation than somatic cells , f2 ?4 I8 d. @8 K1 l3 H- \•Degree of abnormality differs more between hESC lines than hiPSC lines # N4 Z! b8 ~6 ?7 f/ G. X. W8 j2 V•Deletions common in hiPSCs after reprogramming, duplications appear over time 5 t1 I- D* r9 u( o3 W# J% @* _•Recurrent duplications occur at specific genomic loci in pluripotent cells M @# p0 ?; H3 i( ]' o7 }
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Summary ' u, z3 |3 T4 I( V; O9 g# R7 v4 iGenomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells. We performed high-resolution SNP (single-nucleotide polymorphism) analysis on 186 pluripotent and 119 nonpluripotent samples. We report a higher frequency of subchromosomal copy number variations in pluripotent samples compared to nonpluripotent samples, with variations enriched in specific genomic regions. The distribution of these variations differed between hESCs and hiPSCs, characterized by large numbers of duplications found in a few hESC samples and moderate numbers of deletions distributed across many hiPSC samples. For hiPSCs, the reprogramming process was associated with deletions of tumor-suppressor genes, whereas time in culture was associated with duplications of oncogenic genes. We also observed duplications that arose during a differentiation protocol. Our results illustrate the dynamic nature of genomic abnormalities in pluripotent stem cells and the need for frequent genomic monitoring to assure phenotypic stability and clinical safety.: U @2 `; A; j. C! H
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人 ESCs 和 iPSCs的多能性和细胞增殖基因在拷贝数上存在动态变化 6 R& W' D" k5 J基因组的稳定性，是人胚胎干细胞（hESCs）和 iPSCs用于临床的关键。本研究采用单核苷酸多态性方法，分析了186个多能性和119个非多能性的细胞样品。研究发现，与非多能性的细胞样品相比，具有多能性的细胞样品在亚染色体的拷贝数存在高频率的变化差异，这些变化集中在特定的基因组区域。在hESCs 和hiPSCs中，这些变化的分布也存在差异，在少量hESC样品中，复制相关基因出现较多拷贝，而在很多hiPSC样品中，复制相关基因出现一定量的缺失。对于hiPSCs来说，它的重编程过程涉及到了肿瘤抑制基因的缺失，在培养过程中，又涉及到致癌基因的复制。研究发现，多能性干细胞的基因组存在动态的异常，为了保证表型的稳定和临床的安全，我们必须定期检测多能性干细胞的基因组。7 L( n+ P) v6 x: b b1 `& {) j
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hESCs和iPSCs的基因组都不稳定啊~~~ips的临床，离我们还是很远~~~因为ips还有很多的未知~~~包括机制和安全~~~ % M4 s1 n9 M3 Q: b ( f( t7 n1 n5 ^9 r5 Z8 {) [, ^8 A 4 ~: D9 L6 J& h1 [6 u
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