Kahney Elizabeth W, Ranjan Rajesh, Gleason Ryan J, Chen Xin
Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218-2685.
Cold Spring Harb Symp Quant Biol. 2017;82:305-318. doi: 10.1101/sqb.2017.82.034272. Epub 2018 Jan 18.
The processes of DNA replication and mitosis allow the genetic information of a cell to be copied and transferred reliably to its daughter cells. However, if DNA replication and cell division were always performed in a symmetric manner, the result would be a cluster of tumor cells instead of a multicellular organism. Therefore, gaining a complete understanding of any complex living organism depends on learning how cells become different while faithfully maintaining the same genetic material. It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program. Nevertheless, how epigenetic information contained in the parental cell is either maintained or changed in the daughter cells remains largely unknown. During the asymmetric cell division (ACD) of male germline stem cells, our previous work revealed that preexisting histones are selectively retained in the renewed stem cell daughter, whereas newly synthesized histones are enriched in the differentiating daughter cell. We also found that randomized inheritance of preexisting histones versus newly synthesized histones results in both stem cell loss and progenitor germ cell tumor phenotypes, suggesting that programmed histone inheritance is a key epigenetic player for cells to either remember or reset cell fates. Here, we will discuss these findings in the context of current knowledge on DNA replication, polarized mitotic machinery, and ACD for both animal development and tissue homeostasis. We will also speculate on some potential mechanisms underlying asymmetric histone inheritance, which may be used in other biological events to achieve the asymmetric cell fates.
DNA复制和有丝分裂过程使细胞的遗传信息得以可靠地复制并传递给子细胞。然而，如果DNA复制和细胞分裂总是以对称方式进行，结果将是一群肿瘤细胞而非多细胞生物体。因此，要全面了解任何复杂的生物体，就取决于了解细胞如何在忠实地维持相同遗传物质的同时变得不同。众所周知，每种细胞类型中包含的独特表观遗传信息定义了其独特的基因表达程序。然而，亲代细胞中包含的表观遗传信息在子代细胞中是如何被维持或改变的，在很大程度上仍然未知。在雄性生殖系干细胞的不对称细胞分裂（ACD）过程中，我们之前的研究表明，预先存在的组蛋白被选择性地保留在更新后的干细胞子代中，而新合成的组蛋白则在分化的子代细胞中富集。我们还发现，预先存在的组蛋白与新合成的组蛋白的随机遗传会导致干细胞丢失和祖细胞生殖细胞瘤表型，这表明程序性组蛋白遗传是细胞记住或重置细胞命运的关键表观遗传因素。在这里，我们将结合当前关于DNA复制、极化有丝分裂机制以及动物发育和组织稳态中的ACD的知识来讨论这些发现。我们还将推测不对称组蛋白遗传背后的一些潜在机制，这些机制可能在其他生物学事件中用于实现不对称细胞命运。
