Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells.
Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells.
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DOI：
10.4061/2010/602068
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发表时间：
2010-05-11
影响因子：
4.3
通讯作者：
Xu XX
中科院分区：
文献类型：
--
作者：
Capo-Chichi CD;Smedberg JL;Rula M;Nicolas E;Yeung AT;Adamo RF;Frolov A;Godwin AK;Xu XX
背景。小鼠胚胎干（ES）细胞可以通过聚集和/或维甲酸（RA）处理在体外分化。体外分化谱系主要为胚外原始内胚层。Dab2、层粘连蛋白、GATA4、GATA5和GATA6在胚胎原始内胚层中表达，并在其谱系承诺中起关键作用。结果。我们发现，在缺乏GATA4或GATA5的情况下，ra诱导的ES细胞原始内胚层分化减少。GATA4(−/−)ES细胞表达更高水平的GATA5、GATA6和肝细胞核因子4 α标记物。GATA5（−/−）胚胎干细胞表达较高水平的早期肝脏发育的α胎蛋白标志物。GATA6(−/−)ES细胞表达更高水平的GATA5以及中胚层和心肌细胞标记物胶原III α -1和原肌球蛋白1 α。因此，GATA6的缺失阻止了内胚层的分化，但促进了中胚层的分化。结论。GATA4、GATA5和GATA6各自传递一种独特的基因表达模式，影响胚胎干细胞的分化。我们发现，通过调节GATA因子，胚胎干细胞可以避免向原始内胚层分化，并在体外形成独特的细胞系。这一发现提供了一种从胚胎干细胞中产生理想细胞类型的潜在方法，对再生细胞治疗有用。
Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment. Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (−/−) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (−/−) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (−/−) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages. Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy.
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影响因子：
5.3
作者：
ARCECI, RJ;KING, AAJ;WILSON, DB
通讯作者：
WILSON, DB
影响因子：
64.8
作者：
BARTOLOMEI, MS;ZEMEL, S;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
影响因子：
3.7
作者：
FOWLER, KJ;MITRANGAS, K;DZIADEK, M
通讯作者：
DZIADEK, M
影响因子：
10.5
作者：
Kuo, CT;Morrisey, EE;Leiden, JM
通讯作者：
Leiden, JM
影响因子：
10.5
作者：
Fujikura, J;Yamato, E;Niwa, H
通讯作者：
Niwa, H