High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Vega, SL; Liu, E; Arvind, V; Bushman, J; Sung, H-J; Becker, ML; Lelièvre, S; Kohn, J; Vidi, P-A; Moghe, PV

Published Date

  • February 2017

Published In

Volume / Issue

  • 351 / 1

Start / End Page

  • 11 - 23

PubMed ID

  • 28034673

Pubmed Central ID

  • PMC5303152

Electronic International Standard Serial Number (EISSN)

  • 1090-2422

International Standard Serial Number (ISSN)

  • 0014-4827

Digital Object Identifier (DOI)

  • 10.1016/j.yexcr.2016.12.018


  • eng