دورية أكاديمية
Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
| العنوان: | Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT |
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| المؤلفون: | Paul, Indranil, Bolzan, Dante, Youssef, Ahmed, Gagnon, Keith A., Hook, Heather, Karemore, Gopal, Oliphant, Michael U. J., Lin, Weiwei, Liu, Qian, Phanse, Sadhna, White, Carl, Padhorny, Dzmitry, Kotelnikov, Sergei, Chen, Christopher S., Hu, Pingzhao, Denis, Gerald V., Kozakov, Dima, Raught, Brian, Siggers, Trevor, Wuchty, Stefan, Muthuswamy, Senthil K., Emili, Andrew |
| المساهمون: | Division of Cancer Prevention, National Cancer Institute |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | A proper understanding of disease etiology will require longitudinal systems-scale reconstruction of the multitiered architecture of eukaryotic signaling. Here we combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twelve omics modalities, i.e., protein abundance from whole-cells, nucleus, exosomes, secretome and membrane; N-glycosylation, phosphorylation; metabolites; mRNA, miRNA; and, in parallel, single-cell transcriptomes. We apply PAMAF in an established in vitro model of TGFβ-induced epithelial to mesenchymal transition (EMT) to quantify >61,000 molecules from 12 omics and 10 timepoints over 12 days. Bioinformatics analysis of this EMT-ExMap resource allowed us to identify; –topological coupling between omics, –four distinct cell states during EMT, –omics-specific kinetic paths, –stage-specific multi-omics characteristics, –distinct regulatory classes of genes, –ligand–receptor mediated intercellular crosstalk by integrating scRNAseq and subcellular proteomics, and –combinatorial drug targets (e.g., Hedgehog signaling and CAMK-II) to inhibit EMT, which we validate using a 3D mammary duct-on-a-chip platform. Overall, this study provides a resource on TGFβ signaling and EMT. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-36122-x |
| الإتاحة: | https://doi.org/10.1038/s41467-023-36122-xTest https://www.nature.com/articles/s41467-023-36122-x.pdfTest https://www.nature.com/articles/s41467-023-36122-xTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.85D767A6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-36122-x |
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