Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell Stem Cell. 2010 Jun 4;6(6):557-67. doi: 10.1016/j.stem.2010.04.018.
Regulation of stem cells depends on both tissue-specific transcriptional regulators and changes in chromatin organization, yet the coordination of these events in endogenous niches is poorly understood. In the Drosophila testis, local JAK-STAT signaling maintains germline and somatic stem cells (GSCs and cyst progenitor cells, or CPCs) in a single niche. Here we show that epigenetic regulation via the nucleosome-remodeling factor (NURF) complex ensures GSC and CPC maintenance by positively regulating JAK-STAT signaling, thereby preventing premature differentiation. Conversely, NURF is not required in early differentiating daughter cells of either lineage. Because three additional ATP-dependent chromatin remodelers (ACF, CHRAC, and dMi-2/NuRD) are dispensable for stem cell maintenance in the testis, epigenetic regulation of stem cells within this niche may rely primarily on NURF. Thus, local signals cooperate with specific chromatin-remodeling complexes in intact niches to coordinately regulate a common set of target genes to prevent premature stem cell differentiation.
干细胞的调控依赖于组织特异性转录调节剂和染色质组织的变化,但内源性龛位中这些事件的协调尚不清楚。在果蝇的睾丸中,局部 JAK-STAT 信号维持生殖细胞和体干细胞(GSCs 和胞质祖细胞或 CPCs)在一个单一的龛位中。在这里,我们发现通过核小体重塑因子(NURF)复合物的表观遗传调控通过正调控 JAK-STAT 信号来确保 GSC 和 CPC 的维持,从而防止过早分化。相反,NURF 在两个谱系的早期分化子细胞中都不需要。由于另外三个 ATP 依赖性染色质重塑剂(ACF、CHRAC 和 dMi-2/NuRD)在睾丸中对干细胞的维持是可有可无的,因此这个龛位中的干细胞的表观遗传调控可能主要依赖于 NURF。因此,局部信号与完整龛位中的特定染色质重塑复合物合作,协调调控一组共同的靶基因,以防止干细胞过早分化。