Scientists at Hong Kong’s Institute of Technology (HKIT) have developed a novel technique that allows simultaneous genomic DNA and RNA sequencing in single cells of both frozen and fresh tissues; using this method, they were able to detect “spies” hiding within rare brain tumour cells and reveal their true identities. This discovery paves the way for future drug target discovery, making it easier to study the most complex and rare tumours.
Important information on the tumor’s genomic and molecular composition, or cellular heterogeneity, which influences the disease pathology and the tumor’s ability to develop drug resistance can be gleaned from sequencing the tumor’s genomic DNA and RNA. Exploring new dimensions of the tumour composition at high resolution by looking at the DNA and RNA together may provide answers to questions not yet fully explained by our current understanding of cancers, such as why tumours relapse or become resistant to treatment. While most accessible clinical cancer samples are stored in frozen biobanked tissues, current technologies have limited applicability to simultaneously perform DNA and RNA sequencing in single cells from these tissues.
Prof. Angela Wu, Associate Professor in the Division of Life Science and the Department of Chemical and Biological Engineering at HKUST, and Dr. Lei Yu, a postdoctoral fellow in Wu’s lab, have developed a new flexible single-cell multi-omic profiling technology called scONE-seq, which can analyse frozen cells and hard-to-obtain cell types like bone and brain. This novel approach can also collect genomic and transcriptomic data from a tumour in a single experiment.
Patients diagnosed with an astrocytoma, a particularly deadly and aggressive form of brain tumour, have a 5-year survival rate of only about 5%. In a patient’s astrocytoma sample, the team used their novel single-cell technology to identify a small and distinct tumour cell subpopulation. Since this particular tumour subset was able to pass as typical brain astrocytes, they eluded detection by conventional tumour sequencing techniques. This’spy’ tumour cell also displayed molecular characteristics linked to drug resistance, suggesting that studying its multifaceted role in tumour progression could yield important insights into the aetiology of the disease and new avenues for therapeutic intervention.
The scONE-seq approach provides a new avenue for discovering drug targets and developing new drugs by identifying rare tumour cells that may be missed by previous approaches and lead to failure to respond to therapy. We intend to continue our work, profiling a larger patient cohort with scONE-seq in the hopes of achieving better clinical translational outcomes in the future.
Clinician scientists Drs. Danny CHAN, Aden CHEN, Ho Keung NG, and Wai Sang POON from Chinese University of Hong Kong and Prince of Wales Hospital worked on this study alongside Prof. Jiguang WANG and his team from HKUST’s Division of Life Science and Department of Chemical and Biological Engineering. Science Advances recently published the findings.