Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden.
Dev Cell. 2017 Nov 6;43(3):332-348.e4. doi: 10.1016/j.devcel.2017.10.004.
Great progress has been made in identifying transcriptional programs that establish stem cell identity. In contrast, we have limited insight into how these programs are down-graded in a timely manner to halt proliferation and allow for cellular differentiation. Drosophila embryonic neuroblasts undergo such a temporal progression, initially dividing to bud off daughters that divide once (type I), then switching to generating non-dividing daughters (type 0), and finally exiting the cell cycle. We identify six early transcription factors that drive neuroblast and type I daughter proliferation. Early factors are gradually replaced by three late factors, acting to trigger the type I→0 daughter proliferation switch and eventually to stop neuroblasts. Early and late factors regulate each other and four key cell-cycle genes, providing a logical genetic pathway for these transitions. The identification of this extensive driver-stopper temporal program controlling neuroblast lineage progression may have implications for studies in many other systems.
在鉴定建立干细胞特性的转录程序方面已经取得了重大进展。相比之下，我们对这些程序如何及时降级以停止增殖并允许细胞分化知之甚少。果蝇胚胎神经母细胞经历了这样的时间进程，最初分裂产生一个分裂一次的子细胞（I 型），然后切换到产生不分裂的子细胞（0 型），最后退出细胞周期。我们鉴定了六个早期转录因子，这些因子驱动神经母细胞和 I 型子细胞的增殖。早期因子逐渐被三个晚期因子取代，这些因子作用于触发 I→0 子细胞增殖转换，并最终停止神经母细胞。早期和晚期因子相互调节，调节四个关键的细胞周期基因，为这些转变提供了一个合乎逻辑的遗传途径。这种广泛的驱动-停止的时间程序控制神经母细胞谱系的发展，可能对许多其他系统的研究具有重要意义。
