A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.
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Abstract | 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. |
Year of Publication | 2016
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Journal | Nat Commun
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Volume | 7
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Pages | 10220
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Date Published | 2016 Jan 06
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ISSN | 2041-1723
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URL | |
DOI | 10.1038/ncomms10220
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PubMed ID | 26732280
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PubMed Central ID | PMC4729820
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Grant list | #F32CA1800586 / CA / NCI NIH HHS / United States
R21AI110787 / AI / NIAID NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
DP2 GM119419 / GM / NIGMS NIH HHS / United States
F32 CA180586 / CA / NCI NIH HHS / United States
U54 CA143874 / CA / NCI NIH HHS / United States
U54CA143874 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States
DP2 OD020839 / OD / NIH HHS / United States
RM1 HG006193 / HG / NHGRI NIH HHS / United States
R21 AI110787 / AI / NIAID NIH HHS / United States
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