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Title: Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography

Abstract

Characterizing relationships between cell structures and functions requires mesoscale mapping of intact cells showing subcellular rearrangements following stimulation; however, current approaches are limited in this regard. Here, we report a unique application of soft x-ray tomography to generate three-dimensional reconstructions of whole pancreatic β cells at different time points following glucose-stimulated insulin secretion. Reconstructions following stimulation showed distinct insulin vesicle distribution patterns reflective of altered vesicle pool sizes as they travel through the secretory pathway. Our results show that glucose stimulation caused rapid changes in biochemical composition and/or density of insulin packing, increased mitochondrial volume, and closer proximity of insulin vesicles to mitochondria. Costimulation with exendin-4 (a glucagon-like peptide-1 receptor agonist) prolonged these effects and increased insulin packaging efficiency and vesicle maturation. This study provides unique perspectives on the coordinated structural reorganization and interactions of organelles that dictate cell responses.

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [4];  [5];  [3]; ORCiD logo [6];  [7]; ORCiD logo [3];  [8]; ORCiD logo [6];  [4]; ORCiD logo [2]; ORCiD logo [9]; ORCiD logo [4]; ORCiD logo [10]
  1. Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA., Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  2. Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA., Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  3. iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  4. Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA., Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  5. Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  6. Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  7. Department of Computer Science, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  8. Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  9. California Institute for Quantitative Biosciences, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  10. Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA., iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); National Natural Science Foundation of China (NSFC)
OSTI Identifier:
1734835
Alternate Identifier(s):
OSTI ID: 1763702
Grant/Contract Number:  
AC02-05CH11231; P41GM103445; R01GM083960; P41GM109824; 31950410543
Resource Type:
Published Article
Journal Name:
Science Advances
Additional Journal Information:
Journal Name: Science Advances Journal Volume: 6 Journal Issue: 50; Journal ID: ISSN 2375-2548
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

White, Kate L., Singla, Jitin, Loconte, Valentina, Chen, Jian-Hua, Ekman, Axel, Sun, Liping, Zhang, Xianjun, Francis, John Paul, Li, Angdi, Lin, Wen, Tseng, Kaylee, McDermott, Gerry, Alber, Frank, Sali, Andrej, Larabell, Carolyn, and Stevens, Raymond C.. Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography. United States: N. p., 2020. Web. https://doi.org/10.1126/sciadv.abc8262.
White, Kate L., Singla, Jitin, Loconte, Valentina, Chen, Jian-Hua, Ekman, Axel, Sun, Liping, Zhang, Xianjun, Francis, John Paul, Li, Angdi, Lin, Wen, Tseng, Kaylee, McDermott, Gerry, Alber, Frank, Sali, Andrej, Larabell, Carolyn, & Stevens, Raymond C.. Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography. United States. https://doi.org/10.1126/sciadv.abc8262
White, Kate L., Singla, Jitin, Loconte, Valentina, Chen, Jian-Hua, Ekman, Axel, Sun, Liping, Zhang, Xianjun, Francis, John Paul, Li, Angdi, Lin, Wen, Tseng, Kaylee, McDermott, Gerry, Alber, Frank, Sali, Andrej, Larabell, Carolyn, and Stevens, Raymond C.. Wed . "Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography". United States. https://doi.org/10.1126/sciadv.abc8262.
@article{osti_1734835,
title = {Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography},
author = {White, Kate L. and Singla, Jitin and Loconte, Valentina and Chen, Jian-Hua and Ekman, Axel and Sun, Liping and Zhang, Xianjun and Francis, John Paul and Li, Angdi and Lin, Wen and Tseng, Kaylee and McDermott, Gerry and Alber, Frank and Sali, Andrej and Larabell, Carolyn and Stevens, Raymond C.},
abstractNote = {Characterizing relationships between cell structures and functions requires mesoscale mapping of intact cells showing subcellular rearrangements following stimulation; however, current approaches are limited in this regard. Here, we report a unique application of soft x-ray tomography to generate three-dimensional reconstructions of whole pancreatic β cells at different time points following glucose-stimulated insulin secretion. Reconstructions following stimulation showed distinct insulin vesicle distribution patterns reflective of altered vesicle pool sizes as they travel through the secretory pathway. Our results show that glucose stimulation caused rapid changes in biochemical composition and/or density of insulin packing, increased mitochondrial volume, and closer proximity of insulin vesicles to mitochondria. Costimulation with exendin-4 (a glucagon-like peptide-1 receptor agonist) prolonged these effects and increased insulin packaging efficiency and vesicle maturation. This study provides unique perspectives on the coordinated structural reorganization and interactions of organelles that dictate cell responses.},
doi = {10.1126/sciadv.abc8262},
journal = {Science Advances},
number = 50,
volume = 6,
place = {United States},
year = {2020},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1126/sciadv.abc8262

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