High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.
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.
['Vega|Sebastián L|SL|', 'Liu|Er|E|', 'Arvind|Varun|V|', 'Bushman|Jared|J|', 'Sung|Hak-Joon|HJ|', 'Becker|Matthew L|ML|', 'Lelièvre|Sophie|S|', 'Kohn|Joachim|J|', 'Vidi|Pierre-Alexandre|PA|', 'Moghe|Prabhas V|PV|']
D017667:Adipocytes D034961:Antigens, Nuclear D018797:Cell Cycle Proteins D002454:Cell Differentiation D002460:Cell Line D002467:Cell Nucleus D002469:Cell Separation D002471:Cell Transformation, Neoplastic D002478:Cells, Cultured D006801:Humans D059630:Mesenchymal Stem Cells D034521:Nuclear Matrix-Associated Proteins D010011:Osteocytes D059010:Single-Cell Analysis
Image informatics Imaging Nuclear Oncogenic transformation Organization Differentiation Mesenchymal stem cells Stem cells Biomaterials