CRISPR筛选鉴定HDAC3为小细胞肺癌新型放疗增敏靶点

数据集获取

源站：https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE280682

标准获取流程：

1. 访问源站链接，注册/登录账号；
2. 进入数据集详情页，按页面指引申请权限或直接下载；
3. 部分平台提供 SDK，例如：
   • OpenDataLab: pip install openxlab 后 openxlab.dataset.get(...)
   • ModelScope: pip install modelscope 后 modelscope download
   • 天池: 登录后页面提供直链下载
     以源站「数据下载/使用文档」页面为准。

数据说明

Small cell lung cancer (SCLC) is an aggressive malignancy, with most patients presenting with prognostically poor extensive-stage disease. Limited progress in standard care stresses the urgent need for novel therapies. Radiotherapy offers some survival benefit for select SCLC patients but could be enhanced with radiosensitizers. Here, we identify HDAC3 as a novel radiosensitizing target in SCLC using a CRISPR knockout screen and demonstrate its efficacy and mechanism. SBC5 cells were transduced with a custom EpiDrug sgRNA library and treated with ionizing radiation (IR). Cells were collected and sequenced at multiple timepoints to identify radiosensitizing genes. To validate this target, HDAC3 functional loss was generated by genetic knockdown (KD) and RGFP966 inhibition in several SCLC cell lines. HDAC3 KD and RGFP966 inhibition increased radiosensitivity, as shown by cell viability (dose[1]modification factor [DMF]10 = 1.14-1.69) and clonogenic assays (DMF10 = 1.16-1.41). We evaluated changes in chromatin accessibility by ATAC-seq, and IR-induced DNA damage and repair using γH2AX foci detection and double-strand break (DSB) repair assays. Cells with HDAC3 functional loss demonstrated increased chromatin accessibility which was associated with more IR-induced DNA DSBs, and impaired DSB repair function leading to persisting DNA damage. In SCLC xenograft models, HDAC3 KD or RGFP966, combined with IR, enhanced radiosensitivity and achieved significant tumor growth inhibition. Taken together, we identified HDAC3 as a novel radiosensitizing target in SCLC. Its functional loss increases the generation and persistence of IR-induced DNA DSBs, effectively sensitizing SCLC cell lines and xenografts to IR, providing a potential radiosensitization strategy to treat SCLC.

数据加载示例（图像类）

from PIL import Image
import glob, os

files = (glob.glob(os.path.join(path, "**", "*.png"), recursive=True)
       + glob.glob(os.path.join(path, "**", "*.jpg"), recursive=True)
       + glob.glob(os.path.join(path, "**", "*.tif"), recursive=True))
print("图像文件数:", len(files))
img = Image.open(files[0]); print("尺寸/模式:", img.size, img.mode)

# torchvision Dataset 方式:
# from torchvision import datasets
# ds = datasets.ImageFolder(path)  # 要求 子目录=类别

目录组织与标注格式以源站说明和下载后实际文件为准。