Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression
Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression
ABSTRACT Sequencing the genomes of individual cancer cells provides the highest resolution of intratumoral heterogeneity. To enable high throughput single cell DNA-Seq across thousands of individual cells per sample, we developed a droplet-based, automated partitioning technology for whole genome sequencing. We applied this approach on a set of gastric cancer cell lines and a primary gastric tumor. In parallel, we conducted a separate single cell RNA-Seq analysis on these same cancers and used copy number to compare results. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection – where the percentage of replicating cells per clone is higher than expected – indicating ongoing tumor evolution. Our study demonstrates that joining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.
Song Maengseok、Lau Billy T.、Catalanotti Claudia、Kumar Vijay、Belhocine Kamila、Stafford David、Jett Susana、Lin Bill Kengli、Makarewicz Anthony J.、Rahimi Mohammad、Sauzade Martin、Shuga Joe、Yin Yifeng、Chen Jiamin、Grimes Susan M.、Suarez Carlos Jose、Poultsides George A.、Schnall-Levin Michael、Andor Noemi、Price Andrew D.、Sawhney Sanjam S.、DeMare Laura、Sullivan-Bibee Katrina、Bharadwaj Rajiv、Maheshwari Shamoni、Ji Hanlee P.、Hepler Lance、Sathe Anuja、Wheeler Tobias D.、Kubit Matthew A.、Yang Wei、Bent Zachary、Weinstein Adam
10X GenomicsStanford Genome Technology Center, Stanford University10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X GenomicsDivision of Oncology, Department of Medicine, Stanford University School of MedicineStanford Genome Technology Center, Stanford UniversityDepartment of Pathology, Stanford University School of MedicineDepartment of Surgery, Stanford University School of Medicine10X GenomicsDivision of Oncology, Department of Medicine, Stanford University School of Medicine10X Genomics10X Genomics10X Genomics10X Genomics10X Genomics10X GenomicsDivision of Oncology, Department of Medicine, Stanford University School of Medicine||Stanford Genome Technology Center, Stanford University10X GenomicsDivision of Oncology, Department of Medicine, Stanford University School of Medicine10X GenomicsDivision of Oncology, Department of Medicine, Stanford University School of Medicine10X Genomics10X Genomics10X Genomics
肿瘤学生物科学研究方法、生物科学研究技术细胞生物学
Song Maengseok,Lau Billy T.,Catalanotti Claudia,Kumar Vijay,Belhocine Kamila,Stafford David,Jett Susana,Lin Bill Kengli,Makarewicz Anthony J.,Rahimi Mohammad,Sauzade Martin,Shuga Joe,Yin Yifeng,Chen Jiamin,Grimes Susan M.,Suarez Carlos Jose,Poultsides George A.,Schnall-Levin Michael,Andor Noemi,Price Andrew D.,Sawhney Sanjam S.,DeMare Laura,Sullivan-Bibee Katrina,Bharadwaj Rajiv,Maheshwari Shamoni,Ji Hanlee P.,Hepler Lance,Sathe Anuja,Wheeler Tobias D.,Kubit Matthew A.,Yang Wei,Bent Zachary,Weinstein Adam.Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression[EB/OL].(2025-03-28)[2025-06-15].https://www.biorxiv.org/content/10.1101/445932.点此复制
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