Selective single cell isolation for genomics using microraft arrays

Joshua D. Welch, Lindsay A. Williams, Matthew DiSalvo, Alicia T. Brandt, Raoud Marayati, Christopher E. Sims, Nancy L. Allbritton, Jan F. Prins, Jen Jen Yeh, Corbin D. Jones

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Genomic methods are used increasingly to interrogate the individual cells that compose specific tissues. However, current methods for single cell isolation struggle to phenotypically differentiate specific cells in a heterogeneous population and rely primarily on the use of fluorescent markers. Many cellular phenotypes of interest are too complex to be measured by this approach, making it difficult to connect genotype and phenotype at the level of individual cells. Here we demonstrate that microraft arrays, which are arrays containing thousands of individual cell culture sites, can be used to select single cells based on a variety of phenotypes, such as cell surface markers, cell proliferation and drug response. We then show that a common genomic procedure, RNA-seq, can be readily adapted to the single cells isolated from these rafts. We show that data generated using microrafts and our modified RNA-seq protocol compared favorably with the Fluidigm C1. We then used microraft arrays to select pancreatic cancer cells that proliferate in spite of cytotoxic drug treatment. Our single cell RNA-seq data identified several expected and novel gene expression changes associated with early drug resistance.

Original languageEnglish (US)
Pages (from-to)8292-8301
Number of pages10
JournalNucleic acids research
Issue number17
StatePublished - Sep 30 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.


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