miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation.
miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation.
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DOI：
10.1016/j.stemcr.2018.02.006
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发表时间：
2018-04-10
影响因子：
5.9
通讯作者：
Bellenchi GC
中科院分区：
文献类型：
--
作者：
De Gregorio R;Pulcrano S;De Sanctis C;Volpicelli F;Guatteo E;von Oerthel L;Latagliata EC;Esposito R;Piscitelli RM;Perrone-Capano C;Costa V;Greco D;Puglisi-Allegra S;Smidt MP;di Porzio U;Caiazzo M;Mercuri NB;Li M;Bellenchi GC
多巴胺能神经元的分化需要形态发生素和转录因子在精确和明确的时间窗内协同作用。关于microRNA在这些事件中的潜在作用知之甚少。通过进行microRNA-mRNA配对微阵列筛选，我们在多巴胺能分化过程中最上调的microRNA中鉴定了miR-34 b/c。有趣的是，miR-34 b/c调节Wnt 1表达，促进细胞周期退出，并诱导多巴胺能分化。当与转录因子ASCL 1和miR-34 b/c结合时，miR-34 b/c使转分化成多巴胺能神经元的成纤维细胞的产量加倍。诱导的多巴胺能（iDA）细胞合成多巴胺，并显示自发的电活动，可逆地被河豚毒素阻断，与脑多巴胺能神经元的电生理特性相一致。我们的研究结果指出了miR-34 b/c在神经元定向中的作用，并强调了利用其与关键转录因子的协同作用来增强多巴胺能神经元体外生成的潜力。miR-34 b/c在Pitx 3-GFP+ mDA神经元中富集miR-34 b/c靶向Wnt 1 -3′ UTR miR-34 b/c在mESC的多巴胺能分化过程中表达miR-34 b/c增强成纤维细胞转分化为功能性iDA神经元在这篇文章中，Bellenchi及其同事表明，microRNA miR-34 b/c在FACS纯化的Pitx 3-GFP+中表达。通过负调节Wnt 1和下游WNT信号通路促进多巴胺能神经元分化。表达miR-34 b/c的诱导多巴胺能细胞合成多巴胺，并显示出脑多巴胺能神经元的电生理特性。
The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated microRNAs during dopaminergic differentiation. Interestingly, miR-34b/c modulates Wnt1 expression, promotes cell cycle exit, and induces dopaminergic differentiation. When combined with transcription factors ASCL1 and NURR1, miR-34b/c doubled the yield of transdifferentiated fibroblasts into dopaminergic neurons. Induced dopaminergic (iDA) cells synthesize dopamine and show spontaneous electrical activity, reversibly blocked by tetrodotoxin, consistent with the electrophysiological properties featured by brain dopaminergic neurons. Our findings point to a role for miR-34b/c in neuronal commitment and highlight the potential of exploiting its synergy with key transcription factors in enhancing in vitro generation of dopaminergic neurons. miR-34b/c is enriched in Pitx3-GFP+ mDA neurons miR-34b/c targets Wnt1-3′ UTR miR-34b/c is expressed during dopaminergic differentiation of mESCs miR-34b/c enhances fibroblast transdifferentiation into functional iDA neurons In this article, Bellenchi and colleagues show that the microRNA miR-34b/c is expressed in FACS-purified Pitx3-GFP+ neurons and promotes dopaminergic differentiation by negative modulating Wnt1 and the downstream WNT signaling pathway. Induced dopaminergic cells, expressing miR-34b/c, synthesize dopamine and show the electrophysiological properties featured by brain dopaminergic neurons.
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DOI：
10.1126/science.aad2509
发表时间：
2015-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amin ND;Bai G;Klug JR;Bonanomi D;Pankratz MT;Gifford WD;Hinckley CA;Sternfeld MJ;Driscoll SP;Dominguez B;Lee KF;Jin X;Pfaff SL
通讯作者：
Pfaff SL
影响因子：
5.3
作者：
Davis, Tigwa H.;Cuellar, Trinna L.;Ullian, Erik M.
通讯作者：
Ullian, Erik M.
David Gene功能分类工具：一种以生物模块为中心的新型算法，可在功能上分析大基因列表。
影响因子：
12.3
作者：
Huang, Da Wei;Sherman, Brad T;Tan, Qina;Collins, Jack R;Alvord, W Gregory;Roayaei, Jean;Stephens, Robert;Baseler, Michael W;Lane, H Clifford;Lempicki, Richard A
通讯作者：
Lempicki, Richard A
影响因子：
16.6
作者：
Jiang H;Xu Z;Zhong P;Ren Y;Liang G;Schilling HA;Hu Z;Zhang Y;Wang X;Chen S;Yan Z;Feng J
通讯作者：
Feng J
影响因子：
14.9
作者：
Huang DW;Sherman BT;Tan Q;Kir J;Liu D;Bryant D;Guo Y;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA