人间充质干细胞成骨分化早期HOX家族基因转录的表观遗传调控

人间充质干细胞(human mesenchymal stem cells,hMSCs)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重塑.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.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家族基因的表达水平在hMSCs早期成骨分化过程中显著下降.进一步的研究发现,HOX家族基因的这种表达变化是由其启动子区的组蛋白H3-Lys9乙酰化和二甲基化水平发生变化而导致的.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家族基因表达受到抑制,而这种抑制作用是与其分化过程中发生的染色质重塑事件密切相关的.

The epigenetic regulation of HOX family genes in early osteogenetic differentiation of human mesenchymal stem cells

Mesenchymal stem cells(hMSCs) 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 encodes the class of transcription factors called homeobox,which is spatially and temporally regulated during embryonic development.Induced hMSCs differentiated into osteoblasts,and investigated the expression of the genes of HOX family during the osteogenetic process,the result indicated that the genes of HOX family were down-regulated in the early stage of hMSCs osteogenetic differentiation,which is caused by the change of the histone modification in their promoter regions.The data indicated that the genes in HOX family were repressed in the process of hMSCs differentiation,and the inhibition is closely linked with the reprogramming of chromatin.