Cellular differentiation from human lung epithelial progenitor cells to pulmonary nuroendocrine cells

肺上皮神经内分泌细胞是由人妊娠中期肺内的多能干细胞分化而来。肺神经内分泌细胞分泌儿茶酚胺和神经肽，调节肺上皮细胞的增殖和分化。神经内分泌细胞分化可能与肺部疾病的发病机制有关。我们推测Ash1可能参与调节神经内分泌细胞的分化。为了解肺神经内分泌细胞的作用机制，我们建立了肺上皮多能干细胞向神经内分泌样细胞分化的体外细胞培养体系。胶原基质的相互作用和低氧环境是未成熟肺上皮细胞向神经内分泌细胞分化的重要条件。细胞分化过程中的基因表达谱表明，Ash1的双相上调可能是决定神经内分泌分化的上皮细胞的关键。在这些过程中，Ash1调节靶基因。为了评估Ash1在这一过程中的作用，我们试图产生SiRNA来敲低Ash1 mRNA。Ash1表达的敲低抑制了祖细胞向神经内分泌细胞的细胞分化，并抑制了typrosine羟化酶的转录。我们的研究，现在，正在进行中，以确定阿什1调节基因表达的机制与肺神经内分泌细胞分化。

Lung epithelial neuroendocrine cells are differenciated from multipotent stem cell in lung at the mid term of the pregnancy in human. Pulmonary neuroendocrine cells secret catecholamine and neural peptides, resulting in the regulation of the proliferation and differentiation of lung epithelial cells. It could be possible that neuroendocrine cell differentiation may be associate to pathogenesis of lung diseases. We hypothesized that Ash1 might modulate the differentiation of neuroendocrine cell. To understand the mechanism of pulmonary neuroendocrine cell, we established the in virto cell culture system in which multi-potent stem cell of lung epithelium can differentiate to neuroendocrine-like cells. Interaction collagen matrix and hypoxic condition are important conditions that differentiate the premature pulmonary epithelial cells to neuroendocrine cells. Gene expression profiles under cell differentiation indicated that biphasic up-regulation of Ash1 might be critical for the determination of the epithelial cells for the neuroendocrine differentiation. In these processes, Ash1 regulated the target genes. To assess the role of Ash1 in this process, we tried to produce SiRNA to knockdown Ash1 mRNA. Knockdown of Ash1 expression repressed the cellular differentiation of progenitor cells to neuroendocrine cells and repress typrosine hydroxylase transcription. Our research, now, is ongoing to identify the mechanism of Ash1-regulated gene expression with association to the pulmonary neuroendocrine cell differentiation.