Single-cell RNA-sequencing reveals an intratumor heterogeneity in pancreatic adenocarcinoma [RNA-seq]

We examined the intratumor heterogeneity in S2-VP10 xenograft by single-cell RNA-sequencing. We found a hierarchical tumor progression originating from ROR1high cells with a partial EMT gene signature. We also found that ROR1high cells have the strong capacity as tumor-initiating cells to support tumorigenecity, chemoresistance, and metastasis. CUT&RUN and ATAC-sequencing revealed that ROR1 gene expression is regulated through YAP-BRD4 axis. Together, these data uncover a role for ROR1high cells in tumor progression, suggesting that ablating ROR1high tumor-initiating cells may be the alternative therapeutic strategy in pancreatic adenocarcinoma. Overall design: Examination of RNA-sequencing in (1) ROR1high and ROR1low cells sorted from S2-VP10 xenograft, PDO#1 xenograft, and (2) siRNA against ROR1 transfected PANC-1 cells.