肿瘤细胞的谱系可塑性是Basal型乳腺癌产生肿瘤异质性和抗药性的重要原因。尽管有研究表明Basal型乳腺癌起源于luminal系祖细胞，但对于肿瘤细胞如何获得谱系可塑性，实现从luminal向basal样细胞的转变尚不清楚。此外，可塑性肿瘤细胞具有数量稀少、缺少分子标记的特点，这给研究带来技术难题。. SOX9是重要的干细胞决定因子，对于乳腺上皮细胞逆分化具有重要作用。本项目将以此为出发点，研究SOX9在Basal型乳腺癌发生发展过程中的作用，集中围绕SOX9如何调控肿瘤细胞可塑性、如何影响可塑性肿瘤细胞周围微环境的建立展开探索。我们将结合使用单细胞RNA测序和空间转录组学技术，寻找SOX9影响肿瘤可塑性及其相关微环境的单细胞层面分子机制，为Basal型乳腺癌的治疗提供潜在分子靶点。

Lineage plasticity has been recognized as an important mechanism for the development of tumor heterogeneity and drug resistance in basal-like breast cancer (BLBC), an aggressive cancer subtype. Studies suggest while BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogeneous collection of cells exhibiting basal, luminal and hybrid phenotypes. What drives luminal progenitor cells to acquire lineage plasticity and luminal-to-basal reprogramming remains unclear. Tumor cells with plasticity are often in a very low number and lack of markers, which brings technique obstacles for the study. .SOX9 is an important stem cell determinant and plays an important role in mammary gland epithelial cell dedifferentiation. This project will study the role of SOX9 in BLBC development. The study will focus on how SOX9 regulates the tumor plasticity and the plasticity-related tumor microenvironment. With the newly developed integrating analysis of single-cell RNA-sequencing and spatial transcriptomics, we will explore the molecular mechanisms of SOX9-regulated tumor plasticity at single cell level. Hope new potential cancer therapy targets will be discovered in this study.