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

Robert J Kimmerling; Sanjay M Prakadan; Alejandro J Gupta; Nicholas L Calistri; Mark M Stevens; Selim Olcum; Nathan Cermak; Riley S Drake; Kristine Pelton; Frederik De Smet; Keith L Ligon; Alex K Shalek; Scott R Manalis

doi:10.1186/s13059-018-1576-0

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

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

Authors

Robert J Kimmerling^{1

2}, Sanjay M Prakadan^{1

3

4

5

6}, Alejandro J Gupta^{1

3

4

5

6}, Nicholas L Calistri¹, Mark M Stevens^{1

7}, Selim Olcum¹, Nathan Cermak¹, Riley S Drake^{1

3

4

5

6}, Kristine Pelton⁸, Frederik De Smet⁹, Keith L Ligon⁸, Alex K Shalek^{10

11

12

13

14

15

16}, Scott R Manalis^{17

18

19}

Affiliations

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.

Publication types

Evaluation Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / metabolism
Cell Enlargement*
Cell Line, Tumor
Genomics / methods*
Humans
Lymphocyte Activation
Mice
Microfluidic Analytical Techniques*
Single-Cell Analysis / methods*

Abstract

Publication types

MeSH terms

Grants and funding