Direct lineage conversion of terminally differentiated hepatocytes to functional neurons.
Direct lineage conversion of terminally differentiated hepatocytes to functional neurons.
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DOI：
10.1016/j.stem.2011.09.002
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发表时间：
2011-10-04
期刊：
影响因子：
23.9
通讯作者：
Wernig, Marius
中科院分区：
文献类型：
--
作者：
Marro, Samuele;Pang, Zhiping P.;Yang, Nan;Tsai, Miao-Chih;Qu, Kun;Chang, Howard Y.;Suedhof, Thomas C.;Wernig, Marius
最近的几项研究表明，小鼠和人类成纤维细胞可以直接重编程为诱导神经元（iN）细胞，绕过多能中间状态。然而，成纤维细胞代表了可能含有神经嵴谱系的异质间充质祖细胞，并且起源细胞仍然不确定。这就提出了一个根本性的问题，即在来自不同胚层的细胞类型之间是否可能进行谱系重编程。在这里，我们证明了终末分化的肝细胞可以直接转化为功能性iN细胞。重要的是，单细胞和全基因组表达分析表明，成纤维细胞和肝细胞来源的iN细胞不仅诱导神经元转录程序，而且沉默其供体转录组。剩余的供体特征随时间推移而减少，不能支持功能性肝细胞特性。因此，重编程因子导致二元谱系转换决定，而不是诱导杂交表型，但iN细胞保留其供体细胞的小但可检测的表观遗传记忆。
Several recent studies showed that mouse and human fibroblasts can be directly reprogrammed to induced neuronal (iN) cells, bypassing a pluripotent intermediate state. However, fibroblasts represent heterogeneous mesenchymal progenitor cells that potentially contain neural crest lineages, and the cell of origin remained undefined. This raises the fundamental question whether lineage reprogramming is possible between cell types derived from different germ layers. Here, we demonstrate that terminally differentiated hepatocytes can be directly converted into functional iN cells. Importantly, single cell and genome-wide expression analyses showed that fibroblast- and hepatocyte-derived iN cells not only induced a neuronal transcriptional program, but also silenced their donor transcriptome. The remaining donor signature decreased over time and could not support functional hepatocyte properties. Thus, the reprogramming factors lead to a binary lineage switch decision rather than an induction of hybrid phenotypes but iN cells retain a small but detectable epigenetic memory of their donor cells.
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通过确定的因素将成纤维细胞直接转化为功能性神经元。
影响因子：
64.8
作者：
Vierbuchen, Thomas;Ostermeier, Austin;Pang, Zhiping P.;Kokubu, Yuko;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
9.2
作者：
Horb, ME;Shen, CN;Slack, JMW
通讯作者：
Slack, JMW
DOI：
10.1073/pnas.96.9.5037
发表时间：
1999-04-27
影响因子：
11.1
作者：
Mao, XH;Fujiwara, Y;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
23.9
作者：
Ambasudhan R;Talantova M;Coleman R;Yuan X;Zhu S;Lipton SA;Ding S
通讯作者：
Ding S
影响因子：
64.8
作者：
Yoo, Andrew S.;Sun, Alfred X.;Li, Li;Shcheglovitov, Aleksandr;Portmann, Thomas;Li, Yulong;Lee-Messer, Chris;Dolmetsch, Ricardo E.;Tsien, Richard W.;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.