Transcription factors that convert adult cell identity are differentially polycomb repressed.

Transcription factors that convert adult cell identity are differentially polycomb repressed.
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DOI:
10.1371/journal.pone.0063407
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Eddy SR
Eddy SR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Davis FP;Eddy SR

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能够将一种类型的成体细胞转化为另一种类型的转录因子通常是通过测试在靶细胞中具有已知发育作用的因子而凭经验发现的。在这里,我们表明标准基因组方法(RNA-seq和ChIP-seq)可以帮助识别这些因子,因为大多数在源细胞中被更强烈地抑制,而在靶细胞中表达更高。该标准是一种有效的全基因组筛选,其显著富集可以转分化几种哺乳动物细胞类型的因子,包括神经干细胞、神经元、胰岛和肝细胞。这些结果表明,正如沃丁顿的“表观遗传景观”中所描述的那样,成年细胞类型之间的障碍部分由Polycomb差异抑制的转录因子组成。这种细胞身份的基因组模型有助于使越来越多的转分化方案合理化,并可能有助于促进再生医学的细胞身份工程。
Transcription factors that can convert adult cells of one type to another are usually discovered empirically by testing factors with a known developmental role in the target cell. Here we show that standard genomic methods (RNA-seq and ChIP-seq) can help identify these factors, as most are more strongly Polycomb repressed in the source cell and more highly expressed in the target cell. This criterion is an effective genome-wide screen that significantly enriches for factors that can transdifferentiate several mammalian cell types including neural stem cells, neurons, pancreatic islets, and hepatocytes. These results suggest that barriers between adult cell types, as depicted in Waddington's “epigenetic landscape”, consist in part of differentially Polycomb-repressed transcription factors. This genomic model of cell identity helps rationalize a growing number of transdifferentiation protocols and may help facilitate the engineering of cell identity for regenerative medicine.
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