Correlating mechanical and gene expression data on the single cell level to investigate metastatic phenotypes.

Association analysis Biomechanics Transcriptomics

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
21 Apr 2023
Historique:
received: 01 10 2021
revised: 09 11 2022
accepted: 07 03 2023
medline: 11 4 2023
entrez: 10 4 2023
pubmed: 11 4 2023
Statut: epublish

Résumé

Stiffness has been observed to decrease for many cancer cell types as their metastatic potential increases. Although cell mechanics and metastatic potential are related, the underlying molecular factors associated with these phenotypes remain unknown. Therefore, we have developed a workflow to measure the mechanical properties and gene expression of single cells that is used to generate large linked-datasets. The process combines atomic force microscopy to measure the mechanics of individual cells with multiplexed RT-qPCR gene expression analysis on the same single cells. Surprisingly, the genes that most strongly correlated with mechanical properties were not cytoskeletal, but rather were markers of extracellular matrix remodeling, epithelial-to-mesenchymal transition, cell adhesion, and cancer stemness. In addition, dimensionality reduction analysis showed that cell clustering was improved by combining mechanical and gene expression data types. The single cell genomechanics method demonstrates how single cell studies can identify molecular drivers that could affect the biophysical processes underpinning metastasis.

Identifiants

pubmed: 37034996
doi: 10.1016/j.isci.2023.106393
pii: S2589-0042(23)00470-4
pmc: PMC10074148
doi:

Types de publication

Journal Article

Langues

eng

Pagination

106393

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

The authors declare no competing interest.

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Auteurs

Katherine M Young (KM)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

Congmin Xu (C)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

Kelly Ahkee (K)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

Roman Mezencev (R)

School of Biology, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0405, USA.

Steven P Swingle (SP)

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA 30332-0405, USA.

Tong Yu (T)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

Ava Paikeday (A)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

Cathy Kim (C)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

John F McDonald (JF)

School of Biology, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0405, USA.

Peng Qiu (P)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.

Todd Sulchek (T)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332-0535, USA.
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA 30332-0405, USA.

Classifications MeSH