小鼠肺分支早期发育中肺上皮单细胞的时-空转录组的建立与分析

肺是重要的呼吸器官，是体内外气体交换的重要场所。肺如何进行发育是发育生物学中的核心研究问题之一。肺分支形态建成是肺发育中的重要环节，肺早期分支发育期间的远端-近端模式建立和上皮细胞分化尤为关键。但参与肺早期分支发育远端-近端细胞分化的上皮细胞的异质性尚不够明确，调控基因仍知之尚少。日渐成熟的单细胞转录组学技术为发现稀有细胞类型、研究细胞的动态发育和鉴定基因调控规律提供了高通量研究手段。然而胎鼠肺分支早期发育时期的单细胞转录组学图谱仍属空白。鉴于肺分支早期发育中的远端-近端模式建立和上皮细胞分化具备明显的时空特性，我们尝试在前期研究工作积累之上，开展小鼠肺分支早期发育中肺上皮单细胞的时-空转录组的绘制和分析研究。从而揭示远端-近端发育轴上存在的异质性上皮细胞及其时空分化调控规律，以期为完善肺早期发育研究提供重要的参考和新的研究思路。

The lung is an important respiratory organ and an important place for gas exchange in vivo and in vitro. How the lung grows is a classic and core problem in developmental biology. The morphogenesis of pulmonary branches is an important link in the development of lung. And the establishment of distal-proximal developmental pattern and the differentiation of epithelial cells are particularly important during the early development of pulmonary branches. However, the heterogeneity of epithelial cells involved in the differentiation of distal-proximal cells in the early branching development of lung is not clear enough, and the regulatory genes are still unknown. The single-cell transcriptome technology is getting mature, which provides a high-throughput method for the discovery of rare cell types, the study of cell dynamic development and the identification of gene regulation. However, the single-cell transcriptome landscape of cells during the early branching development of fetal mouse lung remains unstudied. In view of the obvious spatiotemporal characteristics of both the establishment of the distal-proximal pattern and epithelial cell differentiation, we are proposing to profile and analyze the single-cell time-space transcriptome of epithelium during mouse pulmonary branching morphogenesis. Based on the accumulation of our previous research work, we aim to reveal the heterogeneous epithelial cells on the distal-proximal development axis and the gene modules regulating the differentiation of epithelial cells. We believe the expected research results of this proposal would contribute to the study of early lung development.