Correlating cell morphology and stochastic gene expression using fluorescence spectroscopy and GPU-enabled image analysis

POSTER

Abstract

Biological processes at the microscopic level appear stochastic, requiring precise measurement and analytical techniques to determine the nature of the underlying regulatory networks. Single-molecule, single-cell studies of gene expression have provided insights into how cells respond to external stimuli. Recent work has suggested that macroscopic cell properties, such as cell morphology, are correlated with gene expression. Here we present single-cell studies of a signal-activated gene network: Interleukin 4 (IL4) RNA production in rat basophil leukemia (RBL) cells during the allergic response. We fluorescently label individual IL4 RNA transcripts in populations of RBL cells, subject to varying external stimuli. A custom super-resolution microscope is used to measure the number of fluorescently labeled IL4 transcripts in populations of RBL cells on a cell-by-cell basis. To test the hypothesis that cell morphology is connected genotype, we analyze white light images of RBL cells and cross-reference cell morphology with IL4 RNA levels. We find that the activation of RBL cells, determined by white-light imaging, is well correlated with IL4 mRNA expression.

Authors

  • Evan Shapiro

    Department of Physics, University of Colorado Denver, Denver, CO 80217

  • Benjamin Bloom

    Department of Physics, University of Arizona, Tucson, AZ, National Institute for Materials Science, Tsukuba, Japan, The University of Electro-Communications, Tokyo, Langmuir Laboratory, New Mexico Tech, The University of Arizona, Brigham Young University, Department of Physics Colorado State University, Colorado School of Mines, National Renewable Energy Laboratory, University of Colorado Boulder, Principal Investigator, Graduate Student, Colorado State University, SSRL, SLAC, Department of Chemistry and Biochemistry, Brigham Young University, Department of Physics and Astronomy, Brigham Young University, National Tsing Hua University, Hsinchu, Taiwan, Colorado State Univ, JILA, University of Colorado at Boulder, NIST, JILA, University of Colorado at Boulder, Heinrich-Heine-Universitat, Department of Physics, University of Colorado Denver, Denver, CO 80217, Biomedical Engineering, University of Texas at Austin, Austin, TX, The University Centre in Svalbard, Utah State University, Utah Valley University, New Mexico State University, The George Washington University Nuclear Physics Research Group, Institute for Nuclear Physics at the Johannes Gutenberg University of Mainz, None, Colorado State Engineering Research Center, St. Petersburg Electrotechnical University in Saint Petersburg, Russia, University of California San Diego, Argonne National Laboratory, Los Alamos National Laboratory, Imperial College London, Space Dynamics Lab, Utah State University, Physics and CASS, Utah State University, Department of Chemistry, Colorado State University, Fort Collins, CO 80523, Department of Physics, Colorado State University, Fort Collins, CO 80523, Dept. of Electrical, Computer, and Energy Engineering, University of Colorado at Boulder, Dept. of Physics and Astronomy, University of Denver, CU Boulder, RASEI, NREL, University of Colorado, Rutgers, UTK, Joint Institute for Heavy Ion Research \& ORNL, University of Guelph, Insitituto de Estructura de la Materia, University of Toronto, INFN Laboratori Nazionali del Sud, University of York, University of Surrey, TRIUMF, Simon Frasier University, Universdad de Sevilla, Simon Fraser University, Univ of Utah, Univ of Wyoming, New Mexico Tech, GLOBALFOUNDRIES, IBM Systems and Technology Group, IBM Research Division, Irvine Valley College, University of Colorado - Boulder, Department of Physics, Arizona State University, Tempe, AZ, Department of Physics, New Mexico State University, Las Cruces, NM, Department of Physics, University of Michigan, Flint, MI, High Altitude Observatory, JILA, University of Colorado

  • Benjamin Bloom

    Department of Physics, University of Arizona, Tucson, AZ, National Institute for Materials Science, Tsukuba, Japan, The University of Electro-Communications, Tokyo, Langmuir Laboratory, New Mexico Tech, The University of Arizona, Brigham Young University, Department of Physics Colorado State University, Colorado School of Mines, National Renewable Energy Laboratory, University of Colorado Boulder, Principal Investigator, Graduate Student, Colorado State University, SSRL, SLAC, Department of Chemistry and Biochemistry, Brigham Young University, Department of Physics and Astronomy, Brigham Young University, National Tsing Hua University, Hsinchu, Taiwan, Colorado State Univ, JILA, University of Colorado at Boulder, NIST, JILA, University of Colorado at Boulder, Heinrich-Heine-Universitat, Department of Physics, University of Colorado Denver, Denver, CO 80217, Biomedical Engineering, University of Texas at Austin, Austin, TX, The University Centre in Svalbard, Utah State University, Utah Valley University, New Mexico State University, The George Washington University Nuclear Physics Research Group, Institute for Nuclear Physics at the Johannes Gutenberg University of Mainz, None, Colorado State Engineering Research Center, St. Petersburg Electrotechnical University in Saint Petersburg, Russia, University of California San Diego, Argonne National Laboratory, Los Alamos National Laboratory, Imperial College London, Space Dynamics Lab, Utah State University, Physics and CASS, Utah State University, Department of Chemistry, Colorado State University, Fort Collins, CO 80523, Department of Physics, Colorado State University, Fort Collins, CO 80523, Dept. of Electrical, Computer, and Energy Engineering, University of Colorado at Boulder, Dept. of Physics and Astronomy, University of Denver, CU Boulder, RASEI, NREL, University of Colorado, Rutgers, UTK, Joint Institute for Heavy Ion Research \& ORNL, University of Guelph, Insitituto de Estructura de la Materia, University of Toronto, INFN Laboratori Nazionali del Sud, University of York, University of Surrey, TRIUMF, Simon Frasier University, Universdad de Sevilla, Simon Fraser University, Univ of Utah, Univ of Wyoming, New Mexico Tech, GLOBALFOUNDRIES, IBM Systems and Technology Group, IBM Research Division, Irvine Valley College, University of Colorado - Boulder, Department of Physics, Arizona State University, Tempe, AZ, Department of Physics, New Mexico State University, Las Cruces, NM, Department of Physics, University of Michigan, Flint, MI, High Altitude Observatory, JILA, University of Colorado