Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
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成年小鼠肝细胞和B淋巴细胞向神经干细胞的直接谱系转化。
DOI：
10.1016/j.stemcr.2014.10.001
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发表时间：
2014-12-09
影响因子：
5.9
通讯作者：
Jaenisch R
中科院分区：
文献类型：
--
作者：
Cassady JP;D'Alessio AC;Sarkar S;Dani VS;Fan ZP;Ganz K;Roessler R;Sur M;Young RA;Jaenisch R
转录因子的过度表达已被用于直接将体细胞重新编程为一系列其他分化的细胞类型，包括可用于生成神经元和胶质细胞的多潜能神经干细胞(NSCs)。然而，在转分化过程中，维持NSC状态的能力和体细胞供体细胞的特性仍然是两个重要的悬而未决的问题。在这里，我们使用多西环素诱导转录因子的转导来产生稳定的三能神经干细胞。诱导的神经干细胞(INSCs)在没有外源因子表达的情况下保持其特性，在转录、表观遗传和功能上与原代脑源性NSCs相似。重要的是，我们还从包括成熟肝细胞和B细胞在内的多种成体细胞类型中培养出了三能iNSCs。我们的结果表明，通过表达特定的转录因子组合，可以从非外胚层细胞诱导出自我维持的增殖性神经细胞。从体细胞诱导出转基因非依赖的三能神经干细胞H3K27ac增强子图谱表明iNSCs是表观遗传重新编程的全基因组成年肝脏和B细胞系转换为iNSCs使用“二次”系统来自B淋巴细胞iNSCs具有免疫球蛋白基因座重排在本文中，Jaenisch和他的同事产生诱导神经干细胞，在转录，表观遗传，和功能上类似于原始NSCs，通过在成纤维细胞中瞬时过表达转录因子。然后，作者通过诱导来自多种成体细胞类型的三能iNSCs来证明谱系转换，包括具有基因重排的肝细胞和B细胞。
Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors. Transgene-independent tripotent neural stem cells are induced from somatic cells H3K27ac enhancer profiling shows iNSCs are epigenetically reprogrammed genome-wide Adult liver and B cells are lineage converted to iNSCs using a “secondary” system iNSCs derived from B lymphocytes have immuloglobulin loci rearrangements In this article, Jaenisch and colleagues generate induced neural stem cells that are transcriptionally, epigenetically, and functionally similar to primary NSCs by transiently overexpressing transcription factors in fibroblasts. The authors then demonstrate lineage conversion by inducing tripotent iNSCs from multiple adult cell types, including liver cells and B cells with genetic rearrangements.
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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：
23.9
作者：
Thier, Marc;Woersdoerfer, Philipp;Edenhofer, Frank
通讯作者：
Edenhofer, Frank
影响因子：
23.9
作者：
Han, Dong Wook;Tapia, Natalia;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.
影响因子：
64.5
作者：
Hanna, Jacob;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
DOI：
10.1073/pnas.1121003109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Lujan, Ernesto;Chanda, Soham;Wernig, Marius
通讯作者：
Wernig, Marius