ZMBH, DKFZ-ZMBH-Alliance, and CellNetworks, Heidelberg University, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
ZMBH, DKFZ-ZMBH-Alliance, and CellNetworks, Heidelberg University, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Cell Rep. 2018 Feb 20;22(8):1982-1993. doi: 10.1016/j.celrep.2018.01.079.
Stem cells of the Drosophila midgut (ISCs) are the only mitotically dividing cells of the epithelium and, therefore, presumably the only epithelial cells that require functional kinetochores for microtubule spindle attachment during mitosis. The histone variant CENP-A marks centromeric chromatin as the site of kinetochore formation and spindle attachment during mitotic chromosome segregation. Here, we show that centromeric proteins distribute asymmetrically during ISC division. Whereas newly synthesized CENP-A is enriched in differentiating progeny, CENP-C is undetectable in these cells. Remarkably, CENP-A persists in ISCs for weeks without being replaced, consistent with it being an epigenetic mark responsible for maintaining stem cell properties. Furthermore, CENP-A and its loading factor CAL1 were found to be essential for post-mitotic, differentiating cells; removal of any of these factors interferes with endoreduplication. Taken together, we propose two additional roles of CENP-A: to maintain stem cell-unique properties and to regulate post-mitotic cells.
果蝇中肠的干细胞（ISCs）是上皮组织中唯一有丝分裂分裂的细胞，因此，推测在有丝分裂过程中，只有这些上皮细胞需要有功能的动粒微管纺锤体附着。组蛋白变体 CENP-A 将着丝粒染色质标记为动粒形成和有丝分裂染色体分离过程中纺锤体附着的位点。在这里，我们表明，着丝粒蛋白在 ISC 分裂过程中分布不对称。虽然新合成的 CENP-A 在分化后代中富集，但这些细胞中无法检测到 CENP-C。值得注意的是，CENP-A 在 ISC 中持续存在数周而没有被取代，这与其作为维持干细胞特性的表观遗传标记一致。此外，发现 CENP-A 和其加载因子 CAL1 对于有丝分裂后、分化的细胞是必不可少的；去除这些因子中的任何一个都会干扰内复制。综上所述，我们提出了 CENP-A 的另外两个作用：维持干细胞特有的特性和调节有丝分裂后细胞。
