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DOE OSTI · 1998955

Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting

Fulcher, James M.·Markillie, Lye Meng·Mitchell, Hugh D.·Williams, Sarah M.·Engbrecht, Kristin M.·Moore, Ronald J.·Chrisler, William B.·Pasa-Tolic, Ljiljana·Zhu, Ying
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Abstract

Single-cell multiomics provides comprehensive insights into gene regulatory networks, cellular diversity, and temporal dynamics. While tools for co-profiling single-cell genomes, transcriptomes, and epigenomes are available, accessing proteomes in parallel is more challenging. We developed nanoSPLITS (nanodroplet SPlitting for Linked-multimodal Investigations of Trace Samples), an integrated platform that enables global profiling of the transcriptome and proteome from same single cells using RNA sequencing and mass spectrometry-based proteomics, respectively. nanoSPLITS can precisely quantify over 5000 genes, 2000 proteins, and 140 phosphopeptides per single cell and identify candidate cell markers from these modalities. By exploring Cdk1-mediated cell cycle arrest, we demonstrate how nanoSPLITS single-cell multiomics can provide comprehensive cellular characterization with insights into covarying protein/gene clusters, unique phosphorylation events, and mitotic pathways.

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Fulcher, James M., Markillie, Lye Meng, Mitchell, Hugh D., Williams, Sarah M., Engbrecht, Kristin M., Moore, Ronald J., Chrisler, William B., Pasa-Tolic, Ljiljana, Zhu, Ying. 2023-08-28. Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting. https://doi.org/10.2172/1998955

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