Koyanagi Kanako O
Faculty of Information Science and Technology, Hokkaido University, North 14, West 9, Kita-ku, Sapporo 060-0814, Japan.
Gene X. 2019 May 31;3:100021. doi: 10.1016/j.gene.2019.100021. eCollection 2019 Sep.
Revealing the landscape of epigenetic changes in cells during differentiation is important for understanding the development of organisms. In this study, to infer such epigenetic changes during human hematopoiesis, ancestral state estimation based on a phylogenetic tree was applied to map the epigenomic changes in six kinds of histone modifications onto the hierarchical cell differentiation process of hematopoiesis using epigenomes of eight types of differentiated hematopoietic cells. The histone modification changes inferred during hematopoiesis showed that changes that occurred on the branches separating different cell types reflected the characteristics of hematopoiesis in terms of genomic position and gene function. These results suggested that ancestral state estimation based on phylogenetic analysis of histone modifications in differentiated hematopoietic cells could reconstruct an appropriate landscape of histone modification changes during hematopoiesis. Since integration of the inferred changes of different histone modifications could reveal genes with specific histone marks such as active histone marks and bivalent histone marks on each internal branch of cell-type trees, this approach could provide valuable information for understanding the cell differentiation steps of each cell lineage.
揭示细胞分化过程中表观遗传变化的全貌对于理解生物体的发育至关重要。在本研究中，为了推断人类造血过程中的此类表观遗传变化，基于系统发育树的祖先状态估计被应用于利用八种分化造血细胞的表观基因组，将六种组蛋白修饰的表观基因组变化映射到造血的分层细胞分化过程中。造血过程中推断出的组蛋白修饰变化表明，在分离不同细胞类型的分支上发生的变化在基因组位置和基因功能方面反映了造血的特征。这些结果表明，基于分化造血细胞中组蛋白修饰的系统发育分析的祖先状态估计可以重建造血过程中组蛋白修饰变化的适当全貌。由于整合不同组蛋白修饰的推断变化可以揭示在细胞类型树的每个内部分支上具有特定组蛋白标记（如活性组蛋白标记和双价组蛋白标记）的基因，这种方法可以为理解每个细胞谱系的细胞分化步骤提供有价值的信息。
