Unbiased Single-Cell Transcriptome-Proteome Co-Profiling Reveals Malignant Dormancy and Post-Transcriptional Buffering of CTCs
He, L.; Ye, K.; Li, H.; Jiang, L.; Zhang, W.; Dang, K.; Ma, X.; Shen, J.; Dong, Y.; Wang, W.; Wang, H.; Huang, Z.-L.; Huang, Y.; Xiang, N.; Yin, Z.; Zhao, X.
Show abstract
Leptomeningeal metastasis is driven by rare cerebrospinal fluid circulating tumor cells (CSF-CTCs). However, the mechanisms underlying their adaptation to chemotherapeutic stress remain elusive, primarily because transcriptomics alone poorly predicts functional protein states. Here, we present scMAPS, a single-cell multi-omics method that employs magnetic-assisted partitioning cell lysates to enable unbiased transcriptome-proteome co-profiling without loss-prone physical splitting and precision device. By coupling scMAPS with our custom CLEAP (CTC Label-free Enrichment and Accurate Picking) system, we performed the first deep multi-omics profiling of rare clinical CSF-CTCs before and after localized chemotherapy, detecting an average of 2,547 proteins and 7,821 genes per cell. The integrated CLEAP-scMAPS pipeline reveals a coordinated prioritizing survival over proliferation malignant dormancy phenotype and identified post-transcriptional buffering as the primary driver of treatment resistance. Our platform enables the comprehensive molecular phenotyping of rare clinical specimens, providing a highly versatile framework for decoding complex post-transcriptional regulatory networks.
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