Epigenetic Signature of Early Cardiac Regulatory Genes in Native Human Adipose-Derived Stem Cells
Epigenetic Signature of Early Cardiac Regulatory Genes in Native Human Adipose-Derived Stem Cells
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DOI：
10.1007/s12013-013-9610-z
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发表时间：
2013-11-01
影响因子：
2.6
通讯作者：
Giordano, Emanuele
中科院分区：
文献类型：
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作者：
Pasini, Alice;Bonafe, Francesca;Giordano, Emanuele
脂肪源性干细胞（ADSC）是从脂肪抽吸物中分离出来的基质间充质干细胞，它们表现出分化为不同谱系的广泛潜力。表观遗传学在调节谱系特异性基因表达中的作用正在评估中，然而迄今为止，对于人类 ADSC 中心脏特异性转录因子基因的相对重要性几乎一无所知。本研究的目的是研究天然人 ADSC 中涉及 MEF-2C、GATA-4 和 Nkx2.5 的 DNA 启动子甲基化和相关组蛋白修饰。使用甲基化特异性 PCR 发现其启动子转录起始处的 CpG 位点未甲基化。染色质免疫沉淀检测显示总乙酰化 H3 组蛋白 (acH3) 水平较低，H3 组蛋白 (H3K27me3) 中三甲基化赖氨酸 27 水平较高，它们与 GATA-4 和 Nkx2.5 启动子相关，表明它们的转录抑制染色质排列。另一方面，MEF-2C 启动子的情况明显相反。因此，在天然人 ADSC 中证实了 MEF-2C 转录本，但没有证实 GATA-4 和 Nkx2.5 转录本。这些结果表明，这些早期心脏调节基因的染色质排列可以作为干预水平进行探索，以解决人类 ADSC 向心脏谱系的分化问题。
Adipose-derived stem cells (ADSCs) are stromal mesenchymal stem cells isolated from lipoaspirates, and they display a broad potential to differentiate toward different lineages. The role of epigenetics in regulating the expression of their lineage-specific genes is under evaluation, however till date virtually nothing is known about the relative significance of cardiac-specific transcription factor genes in human ADSCs. The aim of this study was to investigate DNA promoter methylation and relevant histone modifications involving MEF-2C, GATA-4, and Nkx2.5 in native human ADSCs. CpG sites at the transcription start in their promoters were found unmethylated using methylation-specific PCR. Chromatin immunoprecipitation assay showed low levels of total acetylated H3 histone (acH3) and high levels of trimethylated lysine 27 in H3 histone (H3K27me3) which were associated with both GATA-4 and Nkx2.5 promoters, indicating their transcriptional repressive chromatin arrangement. On the other hand, the opposite was apparent for MEF-2C promoter. Accordingly, MEF-2C-but not GATA-4 and Nkx2.5-transcripts were evidenced in native human ADSCs. These results suggest that the chromatin arrangement of these early cardiac regulatory genes could be explored as a level of intervention to address the differentiation of human ADSCs toward the cardiac lineage.