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Cell states beyond transcriptomics: integrating structural organization and gene expression in hiPSC-derived cardiomyocytes

Kaytlyn A. Gerbin, Tanya Grancharova, Rory Donovan-Maiye, Melissa C. Hendershott, Jackson Brown, Stephanie Q. Dinh, Jamie L. Gehring, Matthew Hirano, Gregory R. Johnson, Aditya Nath, Angelique Nelson, Charles M. Roco, Alexander B. Rosenberg, M. Filip Sluzewski, Matheus P. Viana, Calysta Yan, Rebecca J. Zaunbrecher, Kimberly R. Cordes Metzler, Vilas Menon, Sean P. Palecek, Georg Seelig, Nathalie Gaudreault, Theo Knijnenburg, Susanne M. Rafelski, Julie A. Theriot, Ruwanthi N. Gunawardane
doi: https://doi.org/10.1101/2020.05.26.081083
Kaytlyn A. Gerbin
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Tanya Grancharova
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Rory Donovan-Maiye
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Melissa C. Hendershott
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Jackson Brown
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Stephanie Q. Dinh
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Jamie L. Gehring
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Matthew Hirano
3Department of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA
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Gregory R. Johnson
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Aditya Nath
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Angelique Nelson
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Charles M. Roco
4Department of Bioengineering, University of Washington, Seattle, WA, USA
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Alexander B. Rosenberg
3Department of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA
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M. Filip Sluzewski
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Matheus P. Viana
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Calysta Yan
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Rebecca J. Zaunbrecher
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Kimberly R. Cordes Metzler
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Vilas Menon
5Department of Neurology, Columbia University Medical Center, New York, NY, USA
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Sean P. Palecek
6Department of Chemical and Biological Engineering, University of Wisconsin – Madison, WI, USA
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Georg Seelig
3Department of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA
7Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA, USA
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Nathalie Gaudreault
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Theo Knijnenburg
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Susanne M. Rafelski
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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Julie A. Theriot
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
8Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA
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Ruwanthi N. Gunawardane
2Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA
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  • For correspondence: rug@alleninstitue.org
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Summary

We present a quantitative co-analysis of RNA abundance and sarcomere organization in single cells and an integrated framework to predict subcellular organization states from gene expression. We used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes expressing mEGFP-tagged alpha-actinin-2 to develop quantitative image analysis tools for systematic and automated classification of subcellular organization. This captured a wide range of sarcomeric organization states within cell populations that were previously difficult to quantify. We performed RNA FISH targeting genes identified by single cell RNA sequencing to simultaneously assess the relationship between transcript abundance and structural states in single cells. Co-analysis of gene expression and sarcomeric patterns in the same cells revealed biologically meaningful correlations that could be used to predict organizational states. This study establishes a framework for multi-dimensional analysis of single cells to study the relationships between gene expression and subcellular organization and to develop a more nuanced description of cell states.

Graphical Abstract Transcriptional profiling and structural classification was performed on human induced pluripotent stem cell-derived cardiomyocytes to characterize the relationship between transcript abundance and subcellular organization.

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Competing Interest Statement

A.B.R, C.R. and G.S. are shareholders of Split Bioscience.

Footnotes

  • https://open.quiltdata.com/b/allencell/tree/aics/integrated_transcriptomics_structural_organization_hipsc_cm/

  • https://github.com/AllenCellModeling/fish_morphology_code

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Cell states beyond transcriptomics: integrating structural organization and gene expression in hiPSC-derived cardiomyocytes
Kaytlyn A. Gerbin, Tanya Grancharova, Rory Donovan-Maiye, Melissa C. Hendershott, Jackson Brown, Stephanie Q. Dinh, Jamie L. Gehring, Matthew Hirano, Gregory R. Johnson, Aditya Nath, Angelique Nelson, Charles M. Roco, Alexander B. Rosenberg, M. Filip Sluzewski, Matheus P. Viana, Calysta Yan, Rebecca J. Zaunbrecher, Kimberly R. Cordes Metzler, Vilas Menon, Sean P. Palecek, Georg Seelig, Nathalie Gaudreault, Theo Knijnenburg, Susanne M. Rafelski, Julie A. Theriot, Ruwanthi N. Gunawardane
bioRxiv 2020.05.26.081083; doi: https://doi.org/10.1101/2020.05.26.081083
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Cell states beyond transcriptomics: integrating structural organization and gene expression in hiPSC-derived cardiomyocytes
Kaytlyn A. Gerbin, Tanya Grancharova, Rory Donovan-Maiye, Melissa C. Hendershott, Jackson Brown, Stephanie Q. Dinh, Jamie L. Gehring, Matthew Hirano, Gregory R. Johnson, Aditya Nath, Angelique Nelson, Charles M. Roco, Alexander B. Rosenberg, M. Filip Sluzewski, Matheus P. Viana, Calysta Yan, Rebecca J. Zaunbrecher, Kimberly R. Cordes Metzler, Vilas Menon, Sean P. Palecek, Georg Seelig, Nathalie Gaudreault, Theo Knijnenburg, Susanne M. Rafelski, Julie A. Theriot, Ruwanthi N. Gunawardane
bioRxiv 2020.05.26.081083; doi: https://doi.org/10.1101/2020.05.26.081083

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