Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, Single-cell RNA-Seq, Mass, Growth, Serial suspended microchannel resonator, Multi-omics, Single cell, T cell activation, Glioblastoma, GBM, Drug response, Microfluidics, Biophysical properties, HETEROGENEITY, GENOME, DIFFERENTIATION, METABOLISM, TARGET, TISSUE, Animals, CD8-Positive T-Lymphocytes, Cell Enlargement, Cell Line, Tumor, Genomics, Humans, Lymphocyte Activation, Mice, Microfluidic Analytical Techniques, Single-Cell Analysis, C14/17/084#54271203, 05 Environmental Sciences, 06 Biological Sciences, 08 Information and Computing Sciences, Bioinformatics

Abstract:

Mass and growth rate are highly integrative measures of cell physiology not discernable via genomic measurements. Here, we introduce a microfluidic platform enabling direct measurement of single-cell mass and growth rate upstream of highly multiplexed single-cell profiling such as single-cell RNA sequencing. We resolve transcriptional signatures associated with single-cell mass and growth rate in L1210 and FL5.12 cell lines and activated CD8+ T cells. Further, we demonstrate a framework using these linked measurements to characterize biophysical heterogeneity in a patient-derived glioblastoma cell line with and without drug treatment. Our results highlight the value of coupled phenotypic metrics in guiding single-cell genomics.