Herpes Simplex Virus-Mediated Expression of Pax3 and MyoD in Embryoid Bodies Results in Lineage-Related Alterations in Gene Expression Profiles
Herpes Simplex Virus-Mediated Expression of Pax3 and MyoD in Embryoid Bodies Results in Lineage-Related Alterations in Gene Expression Profiles
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DOI：
10.1634/stemcells.2008-0417
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Glorioso, Joseph C.
中科院分区：
文献类型：
--
作者：
Craft, April M.;Krisky, David M.;Glorioso, Joseph C.
胚胎干细胞发育成多种细胞谱系的能力为组织修复和再生提供了强大的资源。基因转移提供了一种方法来剖析谱系确定中的复杂事件，但受到当前递送系统的限制。我们设计了一种高效的复制缺陷型单纯疱疹病毒基因转移载体（JD β β），用于稳定和瞬时表达已知参与骨骼肌分化的转录因子Pax 3和MyoD。JD β β介导的每个基因在第4天胚状体（早期中胚层）中的表达导致基因表达谱的独特改变的诱导，包括与肌肉和神经嵴发育相关的已知靶基因的上调，而对照增强的绿色荧光蛋白表达载体相对惰性。这种载体递送系统对于使用基因转移来分析特定基因对调控遗传事件和干细胞向特定谱系的承诺的影响具有很大的希望。干细胞2008;26：3119-3129
The ability of embryonic stem cells to develop into multiple cell lineages provides a powerful resource for tissue repair and regeneration. Gene transfer offers a means to dissect the complex events in lineage determination but is limited by current delivery systems. We designed a high-efficiency replication-defective herpes simplex virus gene transfer vector (JD beta beta) for robust and transient expression of the transcription factors Pax3 and MyoD, which are known to be involved in skeletal muscle differentiation. JD beta beta-mediated expression of each gene in day 4 embryoid bodies (early-stage mesoderm) resulted in the induction of unique alterations in gene expression profiles, including the upregulation of known target genes relevant to muscle and neural crest development, whereas a control enhanced green fluorescent protein expression vector was relatively inert. This vector delivery system holds great promise for the use of gene transfer to analyze the impact of specific genes on both regulatory genetic events and commitment of stem cells to particular lineages. STEM CELLS 2008;26:3119-3129