title: High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.
abstract: Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative "imaging-derived" parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions.
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, United States.
authors.forename: Sebastián L
authors.initials: SL
authors.lastname: Vega
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States.
authors.forename: Er
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States.
authors.forename: Varun
authors.initials: V
authors.lastname: Arvind
authors.affiliation: Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ, United States; School of Pharmacy, University of Wyoming, Laramie, WY, United States.
authors.forename: Jared
authors.initials: J
authors.lastname: Bushman
authors.affiliation: Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ, United States; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States.
authors.forename: Hak-Joon
authors.initials: HJ
authors.lastname: Sung
authors.affiliation: Department of Polymer Science and Engineering, University of Akron, Akron, OH, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Becker
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, IN, United States.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lelièvre
authors.affiliation: Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ, United States.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kohn
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, United States. Electronic address: pvidi@wakehealth.edu.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Vidi
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, United States; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States. Electronic address: moghe@rutgers.edu.
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
mesh_terms: D017667:Adipocytes / Q000166:cytology; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002469:Cell Separation / Q000379:methods; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D010011:Osteocytes / Q000166:cytology; D059010:Single-Cell Analysis / Q000379:methods
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins
keywords: Biomaterials; Differentiation; Image informatics; Imaging; Mesenchymal stem cells; Nuclear; Oncogenic transformation; Organization; Stem cells