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PreprintCited by 3Cell Image Analysis TechniquesGene Regulatory Network AnalysisPluripotent Stem Cells Research

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Colony context and size-dependent compensation mechanisms give rise to variations in nuclear growth trajectories

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Dixon, Julie C., Frick, Christopher L., Leveille, Chantelle L., Garrison, Philip, Lee, Peyton A., Mogre, Saurabh S., Morris, Benjamin, Nivedita, Nivedita, Vasan, Ritvik, Chen, Jianxu, Fraser, Cameron L., Gamlin, Clare R., Harris, Leigh K., Hendershott, Melissa C., Johnson, Graham T., Klein, Kyle N., Oluoch, Sandra A., Thirstrup, Derek J., Sluzewski, M. Filip, Wilhelm, Lyndsay, Yang, Ruian, Toloudis, Daniel M., Viana, Matheus P., Theriot, Julie A., Rafelski, Susanne M.·2024·Cell Systems
DOI 10.1101/2024.06.28.601071PMC PMC12221235

Preprint — published as 10.1016/j.cels.2025.101265

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Abstract

Summary: To investigate the fundamental question of how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we focused on nuclear growth in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days, and developed open-source tools for image and data analysis and an interactive timelapse viewer for exploring quantitative features of nuclear size and shape. We performed a data-driven analysis of nuclear growth variations across timescales. We found that individual nuclear volume growth trajectories arise from short timescale variations attributable to their spatiotemporal context within the colony. We identified a strikingly time-invariant volume compensation relationship between nuclear growth duration and starting volume across the population. Notably, we discovered that inheritance plays a crucial role in determining these two key nuclear growth features while other growth features are determined by their spatiotemporal context and are not inherited.

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Metadata

Authors
Dixon, J. C., Frick, C. L., Leveille, C. L., Garrison, P., Lee, P. A., Mogre, S. S., Morris, B., Nivedita, N., Vasan, R., Chen, J., Fraser, C. L., Gamlin, C. R., Harris, L. K., Hendershott, M. C., Johnson, G. T., Klein, K. N., Oluoch, S. A., Thirstrup, D. J., Sluzewski, M. F., Wilhelm, L., Yang, R., Toloudis, D. M., Viana, M. P., Theriot, J. A., & Rafelski, S. M.
Affiliations
  • Allen Institute for Cell Science (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Rafelski, Susanne M.
ORCID
Venue
Cell Systems
Publisher
openRxiv
Published
2024-06-30
Volume
16
Issue
5
Pages
101265-101265
ISSN
2405-4712 (ISSN-L)
DOI
10.1101/2024.06.28.601071
PMC
PMC12221235
OpenAlex
W4409995174
Cited by
3
References
76
Citations by year
2026: 2 · 2025: 1
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell Systems (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • Howard Hughes Medical Institute
  • Gladstone Institutes
  • Union of Concerned Scientists
  • National Institutes of Health
  • National Human Genome Research Institute (UM1HG011593)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
nuclear growth, nuclear volume, induced pluripotent stem cells, cell colonies, spatio-temporal context, cellular heterogeneity, 3D time-lapse imaging

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