title: Optical High Content Nanoscopy of Epigenetic Marks Decodes Phenotypic Divergence in Stem Cells.
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 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.
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.|Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Neal K
authors.initials: NK
authors.lastname: Bennett
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Devita
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chahar
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Viswanath
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eunjee A
authors.initials: EA
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.|Division of Heath Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Giyoung
authors.initials: G
authors.lastname: Jung
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Shao
authors.affiliation: Department of Polymer Science, University of Akron, Akron, Ohio, USA.
authors.forename: Erin P
authors.initials: EP
authors.lastname: Childers
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Shichong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kulesa
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.affiliation: Department of Polymer Science, University of Akron, Akron, Ohio, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Becker
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Anant
authors.initials: A
authors.lastname: Madabhushi
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Verzi
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.|Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
mesh_terms: D000073537:Biological Variation, Population; D002467:Cell Nucleus / Q000737:chemistry; D002843:Chromatin / Q000737:chemistry; D003584:Cytological Techniques / Q000379:methods*; D044127:Epigenesis, Genetic; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000145:classification* / Q000166:cytology*; D061848:Optical Imaging / Q000379:methods*
chemical_list: D002843:Chromatin