CELL STEM CELL:清华丁胜教授利用内源基因诱导多能性干细胞

2018-01-19 海北 MedSci原创

诱导多能性干细胞的产生通常需要转录因子的外源表达来重新激活多能性基因网络。然而,至今为止,我们还不清楚是否内源性染色质的重塑也能够触发重编程,诱导得到多能干细胞(iPSC)。

诱导多能性干细胞的产生通常需要转录因子的外源表达来重新激活多能性基因网络。然而,至今为止,我们还不清楚是否内源性染色质的重塑也能够触发重编程,诱导得到多能干细胞iPSC)。

为此,来自美国格莱斯顿研究所的研究人员利用CRISPR激活,来精确定位和重塑Oct4Sox2的内源基因位点。有趣的是,研究人员发现,靶向Sox2的单基因座足以重塑和激活Sox2,然后诱导其他多能基因的表达,并且建立多能性网络。Oct4启动子和增强子的同时重塑也能够触发重编程。在这两种情况下都能够建立真正的多能细胞系。最后,研究人员表明,Oct4基因座上的组蛋白乙酰化的靶向操纵也可以启动重编程。

该研究通过对内源基因座的精确表观遗传重构,产生了CRISPR激活的真正的iPSC,并阐明了靶向染色质重塑诱发多能性的机理。


原始出处:

Liu Peng et al. CRISPR-Based Chromatin Remodeling of the Endogenous Oct4 or Sox2 Locus Enables Reprogramming to PluripotencyCell Stem Cell, 2018; DOI: http://dx.doi.org/10.1016/j.stem.2017.12.001


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    2018-01-21 医生2397

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