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

Authors

  • Jessica M. Stiles,

    1. Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
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    • These authors contributed equally to this work.
  • Robert Pham,

    1. Klipsch School of Electrical and Computer Engineering, New Mexico State University, Las Cruces, NM, USA
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    • These authors contributed equally to this work.
  • Rebecca K. Rowntree,

    1. Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
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  • Clarissa Amaya,

    1. Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
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  • James Battiste,

    1. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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  • Laura E. Boucheron,

    1. Klipsch School of Electrical and Computer Engineering, New Mexico State University, Las Cruces, NM, USA
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  • Dianne C. Mitchell,

    1. Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
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  • Brad A. Bryan

    Corresponding author
    1. Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
    • Correspondence

      B. A. Bryan, Center of Excellence in Cancer Research, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, MSB1 Room 2111, El Paso, TX 79905, USA

      Fax: +1 915 783 5222

      Tel: +1 915 783 5235

      E-mail: brad.bryan@ttuhsc.edu

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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.

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