诱导干细胞安全吗？"转自全球基因组的微博"

wangwang1987

诱导干细胞的安全性问题引起了人们对这项技术安全性的质疑。这次研究人员干脆用全基因组测序分析了3个小鼠iPS细胞系中所有的结构变异，包括插入、短InDel、复杂重排等，发现各细胞系只有一两个突变，并不存在反转录转座。证明iPSc的基因组具有较好稳定性。
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Genome Sequencing of Mouse Induced Pluripotent Stem Cells Reveals Retroelement Stability and Infrequent DNA Rearrangement during Reprogramming
, w% j6 h/ G  U7 g9 gAaron R. Quinlan1, 2, 4, Michael J. Boland3, 4, Mitchell L. Leibowitz1, Svetlana Shumilina1, Sidney M. Pehrson3, Kristin K. Baldwin3, ,   and Ira M. Hall1, 2, ,  % l) \; g# ?6 V) U/ C

, |, w, r, T' U  ?1 M1 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA% D( h; h8 R: |7 y& u2 ~
2 Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA) I$ |* B. q4 I
3 Department of Cell Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA0 t% C/ `: g  j* h; D
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Corresponding author/ e2 h' j: @0 N) |# [' T$ w. Q9 K0 R  t
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Corresponding author
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4 These authors contributed equally to this work
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3 j2 z. L5 U" M. H: Y2 Q► Reprogramming can produce iPSCs with few (one or two) de novo structural variants ► Structural variants arise in donor somatic cells and during iPSC generation ► iPSCs harboring de novo mutations contribute to tissues of iPSC-derived mice ► Endogenous retroelements remain inactive during reprogramming) \" K5 J, }* X, o3 j9 J2 Q
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/ ~; v" I1 x" v& }- G! v( [The biomedical utility of induced pluripotent stem cells (iPSCs) will be diminished if most iPSC lines harbor deleterious genetic mutations. Recent microarray studies have shown that human iPSCs carry elevated levels of DNA copy number variation compared with those in embryonic stem cells, suggesting that these and other classes of genomic structural variation (SV), including inversions, smaller duplications and deletions, complex rearrangements, and retroelement transpositions, may frequently arise as a consequence of reprogramming. Here we employ whole-genome paired-end DNA sequencing and sensitive mapping algorithms to identify all classes of SV in three fully pluripotent mouse iPSC lines. Despite the improved scope and resolution of this study, we find few spontaneous mutations per line (one or two) and no evidence for endogenous retroelement transposition. These results show that genome stability can persist throughout reprogramming, and argue that it is possible to generate iPSCs lacking gene-disrupting mutations using current reprogramming methods.
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yangjianhong

谢谢分享！

naturalkillerce

回复 wangwang1987 的帖子! Y0 T4 M  v4 R$ o  G$ @! ^
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不过也重复了，编译新闻见“有研究者认为细胞重编程技术比想象中安全”：http://www.stemcell8.cn/thread-47097-1-1.html。不过，谢谢提供原文啊。

michaelgibh

从这篇文章来看，ips技术还算是比较乐观的，至少在基因结构上没有明显的改变，但仍然有1-2个突变，不知道是为什么。除此之外，对于ips，其基因组结构可能本来就不会发生变化，但是其表观遗传状态择很有可能发生很大变化，不知道最近有没有科学家在研究这个。

seall

虽然iPS解决了干细胞来源问题，但是相对于胚胎干细胞和成体干细胞，ips还存在很多问题，最近有很多这方面的文献报道：如iPS存在表观遗传缺陷，与ES细胞相比iPS细胞中很多基因存在异常表达，iPS保留对起始细胞“记忆”，处于年轻态的ips其实并没有完全脱胎换骨，利用ips定向诱导分化后，发现ips会出轨，而且分化方向可能还是原初组织等。