Optical High Content Nanoscopy of Epigenetic Marks Decodes Phenotypic Divergence in Stem Cells.

Journal Article (Journal Article)

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 post-translational 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.

Full Text

Duke Authors

Cited Authors

  • Kim, JJ; Bennett, NK; Devita, MS; Chahar, S; Viswanath, S; Lee, EA; Jung, G; Shao, PP; Childers, EP; Liu, S; Kulesa, A; Garcia, BA; Becker, ML; Hwang, NS; Madabhushi, A; Verzi, MP; Moghe, PV

Published Date

  • January 4, 2017

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 39406 -

PubMed ID

  • 28051095

Pubmed Central ID

  • PMC5209743

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

International Standard Serial Number (ISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/srep39406


  • eng