Cell Size Contributes to Single-Cell Proteome Variation

Overview

Journal J Proteome Res

Publisher American Chemical Society

Specialty Biochemistry

Date 2023 Nov 1

PMID 37910793

Authors

Michael C Lanz

Lucas Fuentes Valenzuela

Joshua E Elias

Jan M Skotheim

Affiliations

Soon will be listed here.

Abstract

Accurate measurements of the molecular composition of single cells will be necessary for understanding the relationship between gene expression and function in diverse cell types. One of the most important phenotypes that differs between cells is their size, which was recently shown to be an important determinant of proteome composition in populations of similarly sized cells. We, therefore, sought to test if the effects of the cell size on protein concentrations were also evident in single-cell proteomics data. Using the relative concentrations of a set of reference proteins to estimate a cell's DNA-to-cell volume ratio, we found that differences in the cell size explain a significant amount of cell-to-cell variance in two published single-cell proteome data sets.

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References

Regev A, Teichmann S, Lander E, Amit I, Benoist C, Birney E . The Human Cell Atlas. Elife. 2017; 6. PMC: 5762154. DOI: 10.7554/eLife.27041. View

Zatulovskiy E, Lanz M, Zhang S, McCarthy F, Elias J, Skotheim J . Delineation of proteome changes driven by cell size and growth rate. Front Cell Dev Biol. 2022; 10:980721. PMC: 9483106. DOI: 10.3389/fcell.2022.980721. View

Lanz M, Zhang S, Swaffer M, Ziv I, Gotz L, Kim J . Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells. Nat Struct Mol Biol. 2024; 31(12):1859-1871. DOI: 10.1038/s41594-024-01353-z. View

Swaffer M, Kim J, Chandler-Brown D, Langhinrichs M, Marinov G, Greenleaf W . Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size. Mol Cell. 2021; 81(23):4861-4875.e7. PMC: 8642314. DOI: 10.1016/j.molcel.2021.10.007. View

Ginzberg M, Chang N, DSouza H, Patel N, Kafri R, Kirschner M . Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity. Elife. 2018; 7. PMC: 6031432. DOI: 10.7554/eLife.26957. View

Leduc A, Huffman R, Cantlon J, Khan S, Slavov N . Exploring functional protein covariation across single cells using nPOP. Genome Biol. 2022; 23(1):261. PMC: 9756690. DOI: 10.1186/s13059-022-02817-5. View

Jones R, Karkanias J, Krasnow M, Pisco A, Quake S, Salzman J . The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans. Science. 2022; 376(6594):eabl4896. PMC: 9812260. DOI: 10.1126/science.abl4896. View

Cadart C, Monnier S, Grilli J, Saez P, Srivastava N, Attia R . Size control in mammalian cells involves modulation of both growth rate and cell cycle duration. Nat Commun. 2018; 9(1):3275. PMC: 6095894. DOI: 10.1038/s41467-018-05393-0. View

Specht H, Emmott E, Petelski A, Huffman R, Perlman D, Serra M . Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity using SCoPE2. Genome Biol. 2021; 22(1):50. PMC: 7839219. DOI: 10.1186/s13059-021-02267-5. View

10.

Claude K, Bureik D, Chatzitheodoridou D, Adarska P, Singh A, Schmoller K . Transcription coordinates histone amounts and genome content. Nat Commun. 2021; 12(1):4202. PMC: 8270936. DOI: 10.1038/s41467-021-24451-8. View

11.

Lanz M, Zatulovskiy E, Swaffer M, Zhang L, Ilerten I, Zhang S . Increasing cell size remodels the proteome and promotes senescence. Mol Cell. 2022; 82(17):3255-3269.e8. PMC: 9444988. DOI: 10.1016/j.molcel.2022.07.017. View

12.

Wu A, Neff N, Kalisky T, Dalerba P, Treutlein B, Rothenberg M . Quantitative assessment of single-cell RNA-sequencing methods. Nat Methods. 2013; 11(1):41-6. PMC: 4022966. DOI: 10.1038/nmeth.2694. View

13.

Brunner A, Thielert M, Vasilopoulou C, Ammar C, Coscia F, Mund A . Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation. Mol Syst Biol. 2022; 18(3):e10798. PMC: 8884154. DOI: 10.15252/msb.202110798. View

14.

Budnik B, Levy E, Harmange G, Slavov N . SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation. Genome Biol. 2018; 19(1):161. PMC: 6196420. DOI: 10.1186/s13059-018-1547-5. View

15.

Liu Y, Beyer A, Aebersold R . On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell. 2016; 165(3):535-50. DOI: 10.1016/j.cell.2016.03.014. View

16.

Wisniewski J, Hein M, Cox J, Mann M . A "proteomic ruler" for protein copy number and concentration estimation without spike-in standards. Mol Cell Proteomics. 2014; 13(12):3497-506. PMC: 4256500. DOI: 10.1074/mcp.M113.037309. View

17.

Liu X, Yan J, Kirschner M . Cell size homeostasis is tightly controlled throughout the cell cycle. PLoS Biol. 2024; 22(1):e3002453. PMC: 10769027. DOI: 10.1371/journal.pbio.3002453. View

18.

Derks J, Leduc A, Wallmann G, Huffman R, Willetts M, Khan S . Increasing the throughput of sensitive proteomics by plexDIA. Nat Biotechnol. 2022; 41(1):50-59. PMC: 9839897. DOI: 10.1038/s41587-022-01389-w. View

19.

Matzinger M, Muller E, Durnberger G, Pichler P, Mechtler K . Robust and Easy-to-Use One-Pot Workflow for Label-Free Single-Cell Proteomics. Anal Chem. 2023; 95(9):4435-4445. PMC: 9996606. DOI: 10.1021/acs.analchem.2c05022. View

20.

Petelski A, Emmott E, Leduc A, Huffman R, Specht H, Perlman D . Multiplexed single-cell proteomics using SCoPE2. Nat Protoc. 2021; 16(12):5398-5425. PMC: 8643348. DOI: 10.1038/s41596-021-00616-z. View