POSTN+ CAFs Function as Major Interacting Hub of Onco-fetal Reprogramming and Predict Relapse in Hepatocellular Carcinoma
The onco-fetal reprogramming of tumor ecosystem results in recapitulation of fetal developmental signatures in tumor microenvironment, leading to immunosuppressive features. We hypothesized that the onco-fetal cell types colocalize to establish onco-fetal niche within the tumor ecosystem. To investigate this, we employed a new DNA nanoball (DNB)-based spatial transcriptomics technology, Stereo-seq, which allows to capture mRNA from spot size of 220nm diameter and 500nm center-to-center distance, enabling unprecedented spatial resolution. We profiled two HCC tumor tissues (HCC01 and HCC03) and segmented the data into 100*100 DNB bins (bin 100 resolution, ~50μm diameter). We also found the association between onco-fetal ecosystem, and relapse in HCC. In order to systematically comprehend the differences between relapsed and non-relapsed ecosystems, we employed NanoString GeoMx digital spatial profiling (DSP) whole transcriptome (~18,000 genes). In total, we profiled 72 regions of interests (ROIs) from 6 slides, including 2 slides of fetal liver.