Quick Commitment and Efficient Reprogramming Route of Direct Induction of Retinal Ganglion Cell-like Neurons.
Quick Commitment and Efficient Reprogramming Route of Direct Induction of Retinal Ganglion Cell-like Neurons.
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直接诱导视网膜神经节细胞样神经元的快速投入和高效重编程途径
DOI：
10.1016/j.stemcr.2020.09.008
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发表时间：
2020-11-10
影响因子：
5.9
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Wang J;He Q;Zhang K;Sun H;Zhang G;Liang H;Guo J;Hao L;Ke J;Chen S
直接重编程已经被广泛探索以产生用于神经生物学研究和转化医学应用的各种类型的神经元，但是仍然没有有效的重编程方法来产生视网膜神经节细胞（RGC）样神经元，其是视网膜中唯一的投射神经元。在这里，我们表明，三个转录因子，Ascl1，Brn3b和Isl1，有效地将成纤维细胞转化为RGC样神经元（iRGCs）。此外，我们表明，细胞进入iRGC重编程途径的能力是由细胞周期状态在该过程的非常早期阶段决定的。iRGC重编程途径涉及中间状态，其特征在于瞬时炎症样应答，随后是活性表观基因组和转录修饰。我们的研究提供了一种有效的方法来产生iRGC，这将是一个有价值的细胞来源，潜在的青光眼细胞替代治疗和药物筛选研究，并揭示了关键的细胞事件，管理成功的神经元命运重编程。Ascl1+Brn3b+Isl1有效地将成纤维细胞重编程为iRGC iRGC重编程途径是早期的，这是由细胞周期状态决定的iRGC重编程途径涉及中间状态在这篇文章中，Chen和同事们表明Ascl1+Brn3b+Isl1转录因子组合有效地将成纤维细胞重编程为iRGC。作者进一步表明，iRGC重编程途径是早期提交的，这是由当时的细胞周期状态决定的，并且iRGC重编程途径涉及以瞬时炎症样反应和活性表观基因组和转录修饰为特征的中间状态。
Direct reprogramming has been widely explored to generate various types of neurons for neurobiological research and translational medicine applications, but there is still no efficient reprogramming method to generate retinal ganglion cell (RGC)-like neurons, which are the sole projection neurons in the retina. Here, we show that three transcription factors, Ascl1, Brn3b, and Isl1, efficiently convert fibroblasts into RGC-like neurons (iRGCs). Furthermore, we show that the competence of cells to enter iRGC reprogramming route is determined by the cell-cycle status at a very early stage of the process. The iRGC reprogramming route involves intermediate states that are characterized by a transient inflammatory-like response followed by active epigenomic and transcriptional modifications. Our study provides an efficient method to generate iRGCs, which would be a valuable cell source for potential glaucoma cell replacement therapy and drug screening studies, and reveals the key cellular events that govern successful neuronal fate reprogramming. Ascl1+Brn3b+Isl1 efficiently reprograms fibroblasts into iRGCs iRGC reprogramming route is committed early, which is determined by cell-cycle status iRGC reprogramming route involves intermediate states In this article, Chen and colleagues show that Ascl1+Brn3b+Isl1 transcription factor combination efficiently reprograms fibroblasts into iRGCs. The authors further show that the iRGC reprogramming route is committed early, which is determined by the cell-cycle status at the time, and that the iRGC reprogramming route involves intermediate states that are characterized by transient inflammatory-like response and active epigenomic and transcriptional modifications.
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影响因子：
25
作者：
Blanchard, Joel W.;Eade, Kevin T.;Szucs, Attila;Lo Sardo, Valentina;Tsunemoto, Rachel K.;Williams, Daniel;Sanna, Pietro Paolo;Baldwin, Kristin K.
通讯作者：
Baldwin, Kristin K.
影响因子：
3.7
作者：
Li R;Wu F;Ruonala R;Sapkota D;Hu Z;Mu X
通讯作者：
Mu X
影响因子：
23.9
作者：
Gascon, Sergio;Murenu, Elisa;Goetz, Magdalena
通讯作者：
Goetz, Magdalena
影响因子：
2.7
作者：
Gan, L;Wang, SW;Klein, WH
通讯作者：
Klein, WH
DOI：
10.1073/pnas.98.4.1649
发表时间：
2001-02-13
影响因子：
11.1
作者：
Liu, W;Mo, ZQ;Xiang, MQ
通讯作者：
Xiang, MQ