Epigenetic Marks Define the Lineage and Differentiation Potential of Two Distinct Neural Crest-Derived Intermediate Odontogenic Progenitor Populations
Epigenetic Marks Define the Lineage and Differentiation Potential of Two Distinct Neural Crest-Derived Intermediate Odontogenic Progenitor Populations
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DOI：
10.1089/scd.2012.0711
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发表时间：
2013-06-01
影响因子：
4
通讯作者：
Diekwisch, Thomas G. H.
中科院分区：
文献类型：
--
作者：
Gopinathan, Gokul;Kolokythas, Antonia;Diekwisch, Thomas G. H.
表观遗传机制，如组蛋白修饰，在间充质干细胞的分化和谱系定型中起着积极的作用。在本研究中，表观遗传状态和分化的两个牙源性神经嵴衍生的中间祖细胞群体：牙髓（DP）和牙囊（DF）进行了比较。ChIP芯片检测显示大量的H3 K27 me 3介导的成牙本质细胞谱系基因DSPP和牙本质基质蛋白1（DMP 1）的抑制在DF细胞，但在DP细胞。与DF细胞相比，矿化诱导条件导致DP细胞中矿化和图案化基因表达水平急剧增加。相反，矿化诱导导致DF细胞中的高度动态组蛋白修饰反应，而DP细胞中只有减弱的作用。DF和DP祖细胞均在早期矿化基因RUNX 2、MSX 2和DLX 5的启动子上具有H3 K4 me 3活性标记，而OSX、IBSP和BG 410启动子富集H3 K9 me 3或H3 K27 me 3。与DF细胞相比，DP细胞表达更高水平的三个多能性相关基因，OCT 4，NANOG和SOX 2。最后，DP和DF细胞独特的二价标记的基因本体比较突出了DP细胞中的细胞-细胞附着基因和DF细胞中的神经发生基因。总之，本研究表明，DF中间牙源性神经嵴谱系区别于DP对应的DSPP和DMP 1基因的表观遗传抑制，并通过动态组蛋白富集矿化诱导。这里提出的研究结果强调了表观遗传调控机制在牙源性神经嵴谱系的终末分化中的重要作用。
Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.