A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages

Biology Biology
Genomics Genomics
Immunology Immunology
Technology Technology
Alex Genshaft Alex Genshaft
Alex K. Shalek Alex K. Shalek
Sam Kazer Sam Kazer

Kimmerling et al.▾ Kimmerling, R.J., Szeto, G.L., Li, J.W., Genshaft, A.S., Kazer, S.W., Payer, K.R., Borrajo J.de R., Blainey, P.C., Irvine D.J., Shalek, A.K., Manalis, S.R.

Nat. Commun. , Volume 7

January, 2016


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.