Tauc Helen Marie, Tasdogan Alpaslan, Meyer Patrick, Pandur Petra
Institut für Biochemie und Molekulare Biologie, Universität Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany
Institut für Immunologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
Development. 2017 Feb 15;144(4):612-623. doi: 10.1242/dev.142703.
Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In , intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs. We show that Nipped-A is required for maintaining the proliferative capacity of ISCs during aging and in response to tissue-damaging or tumorigenic stimuli. Interestingly, Myc cannot compensate for the effect of the loss of Nipped-A on ISC proliferation. Nipped-A seems to be a superordinate regulator of ISC proliferation, possibly by coordinating different processes including modifying the chromatin landscape of ISCs and progenitors.
成体干细胞在静止状态和活跃状态之间维持着微妙的平衡,这种平衡的失调会导致与年龄相关的疾病,如癌症。在肠道中,肠道干细胞(ISC)的增殖受到严格调控,调控失误会损害肠道内环境稳定。已知多种因素可调控ISC的行为;然而,衰老过程中ISC的转录变化仍不清楚。对年轻和年老ISC进行的RNA测序新发现了组蛋白乙酰转移酶复合物的一个亚基Nipped-A,它是ISC增殖的调节因子,在年老ISC中上调。我们发现,Nipped-A是衰老过程中以及应对组织损伤或致瘤刺激时维持ISC增殖能力所必需的。有趣的是,Myc无法补偿Nipped-A缺失对ISC增殖的影响。Nipped-A似乎是ISC增殖的上级调节因子,可能是通过协调不同过程,包括改变ISC和祖细胞的染色质状态。