Optical High Content Nanoscopy of Epigenetic Marks Decodes Phenotypic Divergence in Stem Cells
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srep39406.pdf
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Author(s)
Kim, Joseph J.
Bennett, Neal K.
Devita, Mitchel S.
Chahar, Sanjay
Viswanath, Satish
Lee, Eunjee A.
Shao, Paul P.
Childers, Erin P.
Liu, Shichong
Garcia, Benjamin A.
Date Issued
January 2017
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Kim, Joseph J. et al. “Optical High Content Nanoscopy of Epigenetic Marks Decodes Phenotypic Divergence in Stem Cells.” Scientific Reports 7 (January 2017): 39406 © 2017 The Author(s)
Version
Final published version
Abstract
While distinct stem cell phenotypes follow global changes in chromatin marks, single-cell chromatin technologies are unable to resolve or predict stem cell fates. We propose the first such use of optical high content nanoscopy of histone epigenetic marks (epi-marks) in stem cells to classify emergent cell states. By combining nanoscopy with epi-mark textural image informatics, we developed a novel approach, termed EDICTS (Epi-mark Descriptor Imaging of Cell Transitional States), to discern chromatin organizational changes, demarcate lineage gradations across a range of stem cell types and robustly track lineage restriction kinetics. We demonstrate the utility of EDICTS by predicting the lineage progression of stem cells cultured on biomaterial substrates with graded nanotopographies and mechanical stiffness, thus parsing the role of specific biophysical cues as sensitive epigenetic drivers. We also demonstrate the unique power of EDICTS to resolve cellular states based on epi-marks that cannot be detected via mass spectrometry based methods for quantifying the abundance of histone posttranslational modifications. Overall, EDICTS represents a powerful new methodology to predict single cell lineage decisions by integrating high content super-resolution nanoscopy and imaging informatics of the nuclear organization of epi-marks.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution 4.0 International
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DOI of Published Version
https://doi.org/10.1038/srep39406
