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Integrated measurement of intracellular proteins and transcripts in single cells

Xu, Alexander M. and Liu, Qianhe and Takata, Kaitlyn L. and Jeoung, Sarah and Su, Yapeng and Antoshechkin, Igor and Chen, Sisi and Thomson, Matthew and Heath, James R. (2018) Integrated measurement of intracellular proteins and transcripts in single cells. Lab on a Chip, 18 (21). pp. 3251-3262. ISSN 1473-0197. PMCID PMC6752714. https://resolver.caltech.edu/CaltechAUTHORS:20180910-090801725

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1039/c8lc00639cDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752714PubMed CentralArticle
ORCID:
AuthorORCID
Xu, Alexander M.0000-0003-4877-4358
Liu, Qianhe0000-0002-7517-4772
Takata, Kaitlyn L.0000-0003-4864-9741
Antoshechkin, Igor0000-0002-9934-3040
Heath, James R.0000-0001-5356-4385
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.
Funders:
Funding AgencyGrant Number
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
NIH1U54 CA199090-01
Jean Perkins FoundationUNSPECIFIED
Ben and Catherine Ivy FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
NIHDP5 OD012194
NIH Postdoctoral FellowshipF32CA213966
Issue or Number:21
PubMed Central ID:PMC6752714
Record Number:CaltechAUTHORS:20180910-090801725
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180910-090801725
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89477
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Sep 2018 16:57
Last Modified:29 Oct 2019 22:38

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