Single-cell transcriptomic survey of adenomatous polyposis patients with germline APC mutations

Patients with germline APC mutations are recognized by hundreds of adenoma polyps in colon, which will give rise to adenocarcinoma inevitably. Over 700 germline APC mutations have been reported to be the leading cause of adenomatous polyposis. However, the underlying mechanism of APC mutation triggered colonic cancer remains mysterious. Here, using a modified STRT-seq protocol, we analyzed over 4000 single cells from the four matching adenomatous polyposis, adenocarcinoma, adjacent normal colon tissue and one lymphatic metastasis from four adenomatous polyposis patients with APC mutations. We identified the main cell types existed in human intestine such as B cells, mast cells, T cells, macrophage cells, endothelial cells, stromal cells and epithelial cells. And the proportional changes of various cell types during the development of adenoma were showed. The transcriptomic similarities and differences between adenoma, adenocarcinoma and adjacent normal tissue were comprehensively investigated. For better understanding the tumor progression process, we also take advantage of other genomic signatures, such as SNV and CNV. We found that the gene expression signatures of adenoma and adenocarcinoma were largely similar when compared with adjacent normal tissue. But the mutation accumulation was indeed observed during the progression from adenoma to adenocarcinoma. To summarized, our work will help us accurately investigate the pathogenic mechanism and heterogeneity of APC inactive mutation triggered colonic cancer, which will also help us better understand the non-familial colorectal cancers Overall design: Single cell transcriptome profiles of matching adenomatous polyposis, adenocarcinoma, adjacent normal colon tissue and one lymphatic metastasis from four adenomatous polyposis patients with APC mutations were generated by next generation sequencing using illumina 4000. For each sample, we also extracted the genomic DNA for whole genome sequencing by using illumina 4000. Please note that the *txt files (linked to each sample records) provide the barcode sequence and corrsponding sample names. For example, file 'FAP3_SA_R2.txt' provided the barcode sequence and sample names for FAP3_SA_R2_*fastq.gz.