ArticleProceedings of the National Academy of Sciences of the United States of America2006
Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics.The Journal of cell biology · 2020Article
- Tissue-specific expression of ribosomal protein paralogue eRpL22-like in Drosophila melanogaster eye development.Developmental dynamics : an official publication of the American Association of Anatomists · 2020Article
- The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair.Nucleic acids research · 2019Article
- IL-4 promotes stromal cell expansion and is critical for development of a type-2, but not a type 1 immune response.European journal of immunology · 2019Article
- Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention.Frontiers in medicine · 2019Article
- Architecture in 3D cell culture: An essential feature for in vitro toxicology.Toxicology in vitro : an international journal published in association with BIBRA · 2017Review
- High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.Experimental cell research · 2017Article
- Early Prediction of Cancer Progression by Depth-Resolved Nanoscale Mapping of Nuclear Architecture from Unstained Tissue Specimens.Cancer research · 2015Article
- NuMA promotes homologous recombination repair by regulating the accumulation of the ISWI ATPase SNF2h at DNA breaks.Nucleic acids research · 2014Article
- Increasing the Content of High-Content Screening: An Overview.Journal of biomolecular screening · 2014Review
- Rapid and automated multidimensional fluorescence microscopy profiling of 3D human breast cultures.Integrative biology : quantitative biosciences from nano to macro · 2013Article
- Three-dimensional culture of human breast epithelial cells: the how and the why.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Article
- Interconnected contribution of tissue morphogenesis and the nuclear protein NuMA to the DNA damage response.Journal of cell science · 2012Article
- Therapeutic benefit of treatment of stroke with simvastatin and human umbilical cord blood cells: neurogenesis, synaptic plasticity, and axon growth.Cell transplantation · 2012Article
- Isotropic 3D nuclear morphometry of normal, fibrocystic and malignant breast epithelial cells reveals new structural alterations.PloS one · 2012Article
- Gene expression in the third dimension: the ECM-nucleus connection.Journal of mammary gland biology and neoplasia · 2010Review
- Automated quantification of DNA demethylation effects in cells via 3D mapping of nuclear signatures and population homogeneity assessment.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2009Article
- Cell shape regulates global histone acetylation in human mammary epithelial cells.Experimental cell research · 2007Article
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5 authors.
Funding
Abstract
The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently stained nuclear protein NuMA in different mammary phenotypes obtained using 3D cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from 3D confocal images. Prominent features of fluorescently stained NuMA were detected by using a previously undescribed local bright feature analysis technique, and their normalized spatial density was calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features when nonneoplastic cells underwent phenotypically normal acinar morphogenesis. Conversely, we did not detect any reorganization of NuMA during formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating nonneoplastic from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.
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