Lu Yun, Okubo Tadashi, Rawlins Emma, Hogan Brigid L M
Department of Cell Biology, Box 3709, Duke University Medical Center, Durham, NC 27710, USA.
Proc Am Thorac Soc. 2008 Apr 15;5(3):300-4. doi: 10.1513/pats.200710-162DR.
The entire epithelium of the lung is generated from a small pool of undifferentiated progenitor cells. At least during the early stages of development these reside in the distal tips of the embryonic lung. They respond to multiple signals from the surrounding mesenchyme and play a critical role as morphogenetic organizing centers. In addition, they proliferate rapidly and give rise to daughter cells that differentiate into all the specialized epithelial cells types of the newborn lung. Despite the importance of the progenitor cells, we still know relatively little about the mechanisms controlling their proliferation, morphogenesis, and developmental fate. Here, we discuss new data on the potential role of microRNAs in co-coordinately regulating multiple signaling pathways in embryonic progenitor cells. In particular, our recent transgenic experiments suggest that microRNAs encoded by the miR-17-92 cluster positively promote proliferation of epithelial progenitor cells and inhibit their differentiation. We speculate on how this information might be exploited therapeutically in the long term.
肺的整个上皮组织由一小群未分化的祖细胞产生。至少在发育的早期阶段,这些祖细胞位于胚胎肺的远端末梢。它们对来自周围间充质的多种信号作出反应,并作为形态发生组织中心发挥关键作用。此外,它们迅速增殖并产生分化为新生肺所有特化上皮细胞类型的子细胞。尽管祖细胞很重要,但我们对控制其增殖、形态发生和发育命运的机制仍然知之甚少。在这里,我们讨论了关于微小RNA在协调调节胚胎祖细胞中多种信号通路的潜在作用的新数据。特别是,我们最近的转基因实验表明,由miR-17-92簇编码的微小RNA正向促进上皮祖细胞的增殖并抑制其分化。我们推测从长远来看,这些信息如何在治疗中得到利用。