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Published November 7, 2018 | Supplemental Material + Accepted Version
Journal Article Open

Integrated measurement of intracellular proteins and transcripts in single cells


Biological function arises from the interplay of proteins, transcripts, and metabolites. An ongoing revolution in miniaturization technologies has created tools to analyze any one of these species in single cells, thus resolving the heterogeneity of tissues previously invisible to bulk measurements. An emerging frontier is single cell multi-omics, which is the measurement of multiple classes of analytes from single cells. Here, we combine bead-based transcriptomics with microchip-based proteomics to measure intracellular proteins and transcripts from single cells and defined small numbers of cells. The transcripts and proteins are independently measured by sequencing and fluorescent immunoassays respectively, to preserve their optimal measurement modes, and linked by encoding the physical address locations of the cells into digital sequencing space using spatially patterned DNA barcodes. We resolve cell-type-specific protein and transcript signatures and present a path forward to scaling the platform to high-throughput.

Additional Information

© 2018 The Royal Society of Chemistry. Received 22nd June 2018, Accepted 24th August 2018. First published on 27th August 2018. This study was assisted by the facilities of the Center for High Throughput Single Cell Monitoring and Engineering, the Millard and Muriel Jacobs Genetics and Genomics Laboratory, and the Institute for Systems Biology Sequencing Core. Paul Rivaud, Devdoot Majumdar, Sylvia Plevritis, and Lior Pachter contributed helpful discussions. Q. L., K. L. T., and S. J. were participants of the Caltech Summer Undergraduate Research Fellowship program. Q. L. was supported by the Donald S. Clark SURF Fellowship. The research was funded by U54 NSBCC grant 1U54 CA199090-01, the Jean Perkins Foundation, and the Ben and Catherine Ivy Foundation. M. T. acknowledges support from the Beckman Institute at Caltech and the NIH Office of the Director (OD) NIH DP5 OD012194. A. M. X. is supported by a Ruth L. Kirschstein F32 Postdoctoral Fellowship F32CA213966. Accession numbers: Transcriptome data was deposited in the Sequence Read Archive under Bioproject PRJNA472815. Author contributions: A. M. X., Q. L., K. L. T., S. J., and Y. S. performed experiments. A. M. X., I. A., and J. R. H. designed experiments. A. M. X. and Y. S. analyzed data. A. M. X., S. C., and M. T. developed software. A. M. X. and J. R. H. wrote the manuscript. Conflicts of interest: JRH is a founder and board member of Isoplexis, a company that is seeking to commercialize certain aspects of the SCBC platform.

Attached Files

Accepted Version - nihms-1049039.pdf

Supplemental Material - c8lc00639c1.zip


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