The developmental potential of iPSCs is greatly influenced by reprogramming factor selection.
The developmental potential of iPSCs is greatly influenced by reprogramming factor selection.
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DOI：
10.1016/j.stem.2014.07.003
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发表时间：
2014-09-04
期刊：
影响因子：
23.9
通讯作者：
Jaenisch, Rudolf
中科院分区：
文献类型：
--
作者：
Buganim, Yosef;Markoulaki, Styliani;van Wietmarschen, Niek;Hoke, Heather;Wu, Tao;Ganz, Kibibi;Akhtar-Zaidi, Batool;He, Yupeng;Abraham, Brian J.;Porubsky, David;Kulenkampff, Elisabeth;Faddah, Dina A.;Shi, Linyu;Gao, Qing;Sarkar, Sovan;Cohen, Malkiel;Goldmann, Johanna;Nery, Joseph R.;Schultz, Matthew D.;Ecker, Joseph R.;Xiao, Andrew;Young, Richard A.;Lansdorp, Peter M.;Jaenisch, Rudolf
诱导多能干细胞(IPSCs)通常由Oct4、Sox2、Klf4和Myc(OSKM)转导产生。尽管IPSCs是多能性的，但它们在质量上经常表现出高度的变异，通过嵌合体贡献和四倍体互补在小鼠身上进行衡量。未来的治疗应用将需要可靠的高质量IPSCs。在这里，我们表明IPSC质量的一个主要决定因素是所使用的重新编程因素的组合。基于四倍体互补，我们发现在小鼠胚胎成纤维细胞(MEF)中异位表达Sall4、Nanog、Esrrb和Lin28(SNEL)比其他因素组合(包括OSKM)更有效地产生高质量的IPSCs。尽管高质量品系和低质量品系之间的差异甲基化区域、主调控子的转录数量、特定超级增强子的建立和全球非整倍体是相似的，但基因表达异常、8号染色体三体和异常的H_2A.X沉积是可能也适用于人类的区别特征。
Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A.X deposition were distinguishing features that could potentially also be applicable to human.
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DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Barlow JH;Faryabi RB;Callén E;Wong N;Malhowski A;Chen HT;Gutierrez-Cruz G;Sun HW;McKinnon P;Wright G;Casellas R;Robbiani DF;Staudt L;Fernandez-Capetillo O;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.8
作者：
Boland, Michael J.;Hazen, Jennifer L.;Baldwin, Kristin K.
通讯作者：
Baldwin, Kristin K.
影响因子：
23.9
作者：
Carey, Bryce W.;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf