A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages
Author(s)Li, Jennifer W.; Genshaft, Alex S.; de Riba Borrajo, Jacob; Blainey, Paul C.; Irvine, Darrell J.; Shalek, Alex K.; Manalis, Scott R.; Kimmerling, Robert John; Szeto, Gregory Lee; Kazer, Samuel Weisgurt; Payer, Kristofor Robert; Borrajo, Jacob de Riba; Shalek, Alex; ... Show more Show less
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We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line lineages. Here we report that both cell types have greater intra- than inter-lineage transcriptional similarity. For CD8+ T-cells, genes with functional annotation relating to lymphocyte differentiation and function—including Granzyme B—are enriched among the genes that demonstrate greater intra-lineage expression level similarity. Analysis of gene expression covariance with matched measurements of time since division reveals cell type-specific transcriptional signatures that correspond with cell cycle progression. We believe that the ability to directly measure the effects of lineage and cell cycle-dependent transcriptional profiles of single cells will be broadly useful to fields where heterogeneous populations of cells display distinct clonal trajectories, including immunology, cancer, and developmental biology.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Massachusetts Institute of Technology. Department of Mechanical Engineering; Massachusetts Institute of Technology. Microsystems Technology Laboratories
Nature Publishing Group
Kimmerling, Robert J., Gregory Lee Szeto, Jennifer W. Li, Alex S. Genshaft, Samuel W. Kazer, Kristofor R. Payer, Jacob de Riba Borrajo, et al. “A Microfluidic Platform Enabling Single-Cell RNA-Seq of Multigenerational Lineages.” Nat Comms 7 (January 6, 2016): 10220.
Final published version