miR-373 is regulated by TGFβ signaling and promotes mesendoderm differentiation in human Embryonic Stem Cells.
miR-373 is regulated by TGFβ signaling and promotes mesendoderm differentiation in human Embryonic Stem Cells.
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DOI：
10.1016/j.ydbio.2014.03.020
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发表时间：
2014-07-01
影响因子：
2.7
通讯作者：
Brivanlou, Ali H.
中科院分区：
文献类型：
--
作者：
Rosa, Alessandro;Papaioannou, Marilena D.;Krzyspiak, Joanna E.;Brivanlou, Ali H.
属于进化保守的miR-302家族的microRNA（miRNAs）在胚胎干细胞（ESCs）中发挥重要作用。一些成员的表达，例如人miR-302和小鼠miR-290簇，受到ESC核心转录因子的调节。然而，miRNAs是否在参与人ESC多能性的信号通路下游起作用仍然未知。hESC中多能性的维持受TGFβ途径的控制。在这里，我们表明，抑制该通路的激活素/节点分支影响hESC中一部分miRNA的表达。其中，我们发现了miR-302家族的成员miR-373。适当水平的miR-373对于维持hESC多能性至关重要，因为其过表达导致向中内胚层谱系分化。在参与TGFβ信号传导的miR-373预测靶点中，我们验证了Nodal抑制剂Lefty。我们的工作表明，在胚胎干细胞中miRNA和信号通路之间的相互作用至关重要。
MicroRNAs (miRNAs) belonging to the evolutionary conserved miR-302 family play important functions in Embryonic Stem Cells (ESCs). The expression of some members, such as the human miR-302 and mouse miR-290 clusters, is regulated by ESC core transcription factors. However, whether miRNAs act downstream of signaling pathways involved in human ESC pluripotency remains unknown. The maintenance of pluripotency in hESCs is under the control of the TGFβ pathway. Here, we show that inhibition of the Activin/Nodal branch of this pathway affects the expression of a subset of miRNAs in hESCs. Among them, we found miR-373, a member of the miR-302 family. Proper levels of miR-373 are crucial for the maintenance of hESC pluripotency, since its overexpression leads to differentiation towards the mesendodermal lineage. Among miR-373 predicted targets, involved in TGFβ signaling, we validated the Nodal inhibitor Lefty. Our work suggests a crucial role for the interplay between miRNAs and signaling pathways in ESCs.
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影响因子：
23.9
作者：
Martinez NJ;Gregory RI
通讯作者：
Gregory RI
影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
3.7
作者：
Redshaw N;Camps C;Sharma V;Motallebipour M;Guzman-Ayala M;Oikonomopoulos S;Thymiakou E;Ragoussis J;Episkopou V
通讯作者：
Episkopou V
影响因子：
64.5
作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
通讯作者：
Young RA
影响因子：
23.9
作者：
Lacoste, Arnaud;Berenshteyn, Frada;Brivanlou, Ali H.
通讯作者：
Brivanlou, Ali H.