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Genome Biol. 2018 Nov 27;19(1):207. doi: 10.1186/s13059-018-1576-0.

Linking single-cell measurements of mass, growth rate, and gene expression.

Kimmerling RJ1,2, Prakadan SM1,3,4,5,6, Gupta AJ1,3,4,5,6, Calistri NL1, Stevens MM1,7, Olcum S1, Cermak N1, Drake RS1,3,4,5,6, Pelton K8, De Smet F9, Ligon KL8, Shalek AK10,11,12,13,14,15,16, Manalis SR17,18,19.

Author information

1
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
2
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
3
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA, 02139, USA.
4
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
5
Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
6
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.
8
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
9
Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
10
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. shalek@mit.edu.
11
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA, 02139, USA. shalek@mit.edu.
12
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. shalek@mit.edu.
13
Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. shalek@mit.edu.
14
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. shalek@mit.edu.
15
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. shalek@mit.edu.
16
Massachusetts General Hospital, Boston, MA, 02114, USA. shalek@mit.edu.
17
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. srm@mit.edu.
18
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. srm@mit.edu.
19
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. srm@mit.edu.

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.

KEYWORDS:

Biophysical properties; Drug response; GBM; Glioblastoma; Growth; Mass; Microfluidics; Multi-omics; Serial suspended microchannel resonator; Single cell; Single-cell RNA-Seq; T cell activation

PMID:
30482222
PMCID:
PMC6260722
DOI:
10.1186/s13059-018-1576-0
[Indexed for MEDLINE]
Free PMC Article

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