Morphological restriction of human coronary artery endothelial cells substantially impacts global gene expression patterns

Jessica M. Stiles, Robert Pham, Rebecca K. Rowntree, Clarissa Amaya, James Battiste, Laura E. Boucheron, Dianne C. Mitchell, Brad A. Bryan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Alterations in cell shape have been shown to modulate chromatin condensation and cell lineage specification; however, the mechanisms controlling these processes are largely unknown. Because endothelial cells experience cyclic mechanical changes from blood flow during normal physiological processes and disrupted mechanical changes as a result of abnormal blood flow, cell shape deformation and loss of polarization during coronary artery disease, we aimed to determine how morphological restriction affects global gene expression patterns. Human coronary artery endothelial cells (HCAECs) were cultured on spatially defined adhesive micropatterns, forcing them to conform to unique cellular morphologies differing in cellular polarization and angularity. We utilized pattern recognition algorithms and statistical analysis to validate the cytoskeletal pattern reproducibility and uniqueness of each micropattern, and performed microarray analysis on normal-shaped and micropatterned HCAECs to determine how constrained cellular morphology affects gene expression patterns. Analysis of the data revealed that forcing HCAECs to conform to geometrically-defined shapes significantly affects their global transcription patterns compared to nonrestricted shapes. Interestingly, gene expression patterns were altered in response to morphological restriction in general, although they were consistent regardless of the particular shape the cells conformed to. These data suggest that the ability of HCAECs to spread, although not necessarily their particular morphology, dictates their genomics patterns. Alterations in cell shape affect endothelial cell function, yet it is unknown how morphological restriction affects the transcriptome. We cultured endothelial cells on spatially defined adhesive micropatterns and used pattern recognition algorithms, statistical analysis, and microarray data to demonstrate that the ability of endothelial cells to spread, but not necessarily their particular morphology, dictates their global gene expression patterns.

Original languageEnglish (US)
Pages (from-to)4474-4494
Number of pages21
JournalFEBS Journal
Volume280
Issue number18
DOIs
StatePublished - Sep 2013

Fingerprint

Endothelial cells
Gene expression
Coronary Vessels
Endothelial Cells
Gene Expression
Cell Shape
Microarrays
Adhesives
Pattern recognition
Statistical methods
Blood
Polarization
Physiological Phenomena
Statistical Data Interpretation
Cell Lineage
Transcription
Microarray Analysis
Genomics
Transcriptome
Chromatin

Keywords

  • actin
  • cell morphology
  • coronary artery
  • cytoskeleton
  • endothelial cell
  • genomics
  • image recognition
  • microarray
  • micropatterning

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Stiles, J. M., Pham, R., Rowntree, R. K., Amaya, C., Battiste, J., Boucheron, L. E., ... Bryan, B. A. (2013). Morphological restriction of human coronary artery endothelial cells substantially impacts global gene expression patterns. FEBS Journal, 280(18), 4474-4494. https://doi.org/10.1111/febs.12410

Morphological restriction of human coronary artery endothelial cells substantially impacts global gene expression patterns. / Stiles, Jessica M.; Pham, Robert; Rowntree, Rebecca K.; Amaya, Clarissa; Battiste, James; Boucheron, Laura E.; Mitchell, Dianne C.; Bryan, Brad A.

In: FEBS Journal, Vol. 280, No. 18, 09.2013, p. 4474-4494.

Research output: Contribution to journalArticle

Stiles, JM, Pham, R, Rowntree, RK, Amaya, C, Battiste, J, Boucheron, LE, Mitchell, DC & Bryan, BA 2013, 'Morphological restriction of human coronary artery endothelial cells substantially impacts global gene expression patterns', FEBS Journal, vol. 280, no. 18, pp. 4474-4494. https://doi.org/10.1111/febs.12410
Stiles, Jessica M. ; Pham, Robert ; Rowntree, Rebecca K. ; Amaya, Clarissa ; Battiste, James ; Boucheron, Laura E. ; Mitchell, Dianne C. ; Bryan, Brad A. / Morphological restriction of human coronary artery endothelial cells substantially impacts global gene expression patterns. In: FEBS Journal. 2013 ; Vol. 280, No. 18. pp. 4474-4494.
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