A novel slug-containing negative-feedback loop regulates SCF/c-Kit-mediated hematopoietic stem cell self-renewal.
A novel slug-containing negative-feedback loop regulates SCF/c-Kit-mediated hematopoietic stem cell self-renewal.
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作者：
Zhang Z;Zhu P;Zhou Y;Sheng Y;Hong Y;Xiang D;Qian Z;Mosenson J;Wu WS
SCF/c-Kit通路在控制造血干细胞（HSC）更新中具有关键作用。然而，很少有人知道细胞内调控的SCF/c-Kit途径在HSC。我们在这里报告，鼻涕虫，锌指转录抑制因子，作为一个直接的转录抑制因子的c-Kit的HSC。相反，SCF/c-Kit信号通过下游c-Myc和FoxM 1转录因子正向调节Slug。有趣的是，在Slug缺陷型HSC中，SCF/c-Kit信号传导诱导c-Kit表达。Slug和c-Kit之间的平衡对于维持HSC在体内的再增殖潜力至关重要。总之，我们的研究表明，Slug在HSC中SCF/c-Kit信号通路中的一个新的负反馈调节回路中发挥作用。
The SCF/c-Kit pathway has crucial roles in controlling hematopoietic stem cell (HSC) renewal. However, little is known about the intracellular regulation of the SCF/c-Kit pathway in HSCs. We report here that Slug, a zinc-finger transcription repressor, functions as a direct transcriptional repressor of c-Kit in HSCs. Conversely, SCF/c-Kit signaling positively regulates Slug through downstream c-Myc and FoxM1 transcription factors. Intriguingly, c-Kit expression is induced by SCF/c-Kit signaling in Slug-deficient HSCs. The balance between Slug and c-Kit are critical for maintaining HSC repopulating potential in vivo. Together, our studies demonstrate that Slug functions in a novel negative-feedback regulatory loop in the SCF/c-Kit signaling pathway in HSCs.