Huh Y H, Sherley J L
1] The Adult Stem Cell Technology Center, LLC, Boston, MA, USA [2] Division of Electron Microscopic Research, Korea Basic Science Institute, 169-148 Gwahak-ro, Yuseong-gu, Daejeon, Korea.
The Adult Stem Cell Technology Center, LLC, Boston, MA, USA.
Cell Death Dis. 2014 Dec 4;5(12):e1554. doi: 10.1038/cddis.2014.522.
The role of immortal DNA strands that co-segregate during mitosis of asymmetrically self-renewing distributed stem cells (DSCs) is unknown. Previously, investigation of immortal DNA strand function and molecular mechanisms responsible for their nonrandom co-segregation was precluded by difficulty in identifying DSCs and immortal DNA strands. Here, we report the use of two technological innovations, selective DSC expansion and establishment of H2A.Z chromosomal asymmetry as a specific marker of 'immortal chromosomes,' to investigate molecular properties of immortal chromosomes and opposing 'mortal chromosomes' in cultured mouse hair follicle DSCs. Although detection of the respective suppressive and activating H3K27me3 and H3K4me3 epigenetic marks on immortal chromosomes was similar to randomly segregated chromosomes, detection of both was lower on mortal chromosomes destined for lineage-committed sister cells. This global epigenomic feature of nonrandom co-segregation may reveal a mechanism that maintains an epigenome-wide 'poised' transcription state, which preserves DSC identity, while simultaneously activating sister chromosomes for differentiation.
在不对称自我更新的分布性干细胞（DSC）有丝分裂过程中共同分离的永生DNA链的作用尚不清楚。此前，由于难以识别DSC和永生DNA链，对永生DNA链功能及其非随机共同分离的分子机制的研究受到了阻碍。在此，我们报告利用两项技术创新，即选择性DSC扩增以及将H2A.Z染色体不对称性确立为“永生染色体”的特异性标记，来研究培养的小鼠毛囊DSC中永生染色体和相对的“必死染色体”的分子特性。尽管在永生染色体上检测到的各自的抑制性和激活性H3K27me3和H3K4me3表观遗传标记与随机分离的染色体相似，但在注定要分化为谱系定向姐妹细胞的必死染色体上，两者的检测水平都较低。这种非随机共同分离的整体表观基因组特征可能揭示了一种维持全表观基因组“平衡”转录状态的机制，该机制既能保持DSC的特性，同时又能激活姐妹染色体进行分化。
