Investigate heterogeneous neutrophils in NSCLC

在基因工程小鼠肺腺癌模型中确定SiglecF+中性粒细胞是一个独特的中性粒细胞亚群后，我们成功地建立了一个特异性删除中性粒细胞中SiglecF蛋白的小鼠模型(Ly6G-Cre；SiglecF-Flox)。我们的初步数据显示，在中性粒细胞中敲除SiglecF蛋白后，肿瘤负担增加。我们正在研究这些中性粒细胞的下游变化。同时，我们进行了先进的单细胞RNA测序和单细胞ATAC测序。我们发现了肿瘤相关中性粒细胞在肿瘤微环境(TME)中的发展轨迹，以及驱动这一过程的潜在转录因子。我们还通过CRISPR-Cas9技术建立了一个在中性粒细胞中敲除或过度表达靶蛋白的平台。我们目前正在验证可能调节TME中SiglecF表达和中性粒细胞发育的转录因子。

After identifying SiglecF+ neutrophils as a unique neutrophil subgroup in a genetically engineered mouse model of lung adenocarcinoma, we successfully generated a mouse model specifically deleting SiglecF protein in neutrophils (Ly6G-Cre; SiglecF-flox). Our preliminary data showed an increased tumor burden after knocking out SiglecF protein in neutrophils. We are studying the downstream changes in these groups of neutrophils. Meanwhile, we performed advanced single-cell RNA sequencing with single-cell ATAC sequencing. We discovered the development trajectory of tumor-associated neutrophils in the tumor microenvironment (TME) and potential transcription factors driving this process. We also established a platform to knockout or overexpressed target proteins in neutrophils via CRISPR-Cas9 technology. We are currently validating transcription factors that may regulate SiglecF expression and neutrophil development in TME.