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人间充质干细胞成骨分化早期HOX家族3’端基因转录的表观遗传调控

The Epigenetic Regulation of HOX Family Genes in Early Osteogenetic Differentiation of Human Mesenchymal Stem Cells

【作者】 黄珍东

【导师】 黄百渠; 陆军;

【作者基本信息】 东北师范大学 , 细胞生物学, 2007, 硕士

【摘要】 间充质干细胞(mesenchymal stem cells MSCs)是一类具有多分化潜能的成体干细胞,在体内外可以被人工定向诱导分化成多种不同的细胞。有报道表明在干细胞分化的过程中,细胞核内染色质发生改构。HOX家族基因作为一类转录因子,在胚胎发育以及细胞分化过程中发挥着十分重要作用。本文通过体外定向诱导骨髓间充质干细胞向成骨细胞分化,对比分化前后细胞中HOX家族基因的表达状况,发现HOX家族3’端基因的表达水平在MSCs成骨分化早期是降低的。而通过进一步研究发现,HOX家族3’端基因启动子区的组蛋白H3-Lys9乙酰化下降和二甲基化上升。一系列实验证据表明,在间充质干细胞的成骨分化过程中,HOX家族3’端基因表达受到抑制,而这种抑制作用与其启动子区发生的染色质重塑事件密切相关。

【Abstract】 Mesenchymal stem cells (MSCs) are stromal cells that can be derived from several tissues, such as bone marrow and placenta. They can differentiate into several cell lineages including osteoblasts, chondrocytes, adipocytes and myoblasts in vivo and in vitro. It has been reported that the mammalian chromatin undergoes global remodeling during early development. HOX family encoding the class of transcription factors called homeobox, which is spatially and temporally regulated during embryonic development. We induced MSCs differentiated into osteoblasts,and investigated the expression of the genes in HOX family during the osteogenetic process. We found that the genes in 3’side of HOX family were down-regulated in the early stage of MSCs osteogenetic differentiation, whereas acetylation of H3-lys9 was declined and H3-lys9 methyation was raised in their promoter regions. Our data indicated that the 3’side genes in HOX family are repressed in the process of MSCs differentiated into osteoblasts, and the inhibition is closely linking with the chromatin remodeling.

  • 【分类号】Q343
  • 【下载频次】140
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