دورية أكاديمية
أعرض في EDS

A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.

التفاصيل البيبلوغرافية
العنوان: A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.
المؤلفون: van Groningen T; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Akogul N; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Westerhout EM; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Chan A; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Hasselt NE; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Zwijnenburg DA; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Broekmans M; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Stroeken P; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Haneveld F; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Hooijer GKJ; Department of Pathology, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Savci-Heijink CD; Department of Pathology, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Lakeman A; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Volckmann R; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., van Sluis P; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Valentijn LJ; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Koster J; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Versteeg R; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., van Nes J; Department of Oncogenomics, Amsterdam UMC University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. w.j.vannes@amc.uva.nl.
المصدر: Nature communications [Nat Commun] 2019 Apr 04; Vol. 10 (1), pp. 1530. Date of Electronic Publication: 2019 Apr 04.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Adrenergic Neurons/*pathology , Cellular Reprogramming/*genetics , Mesenchymal Stem Cells/*pathology , Neuroblastoma/*pathology , Receptor, Notch3/*physiology, Adrenergic Neurons/metabolism ; Cell Line, Tumor ; Epigenesis, Genetic ; Feedback, Physiological ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mesenchymal Stem Cells/metabolism ; Neuroblastoma/metabolism ; Receptor, Notch3/genetics ; Receptor, Notch3/metabolism
مستخلص: Transition between differentiation states in development occurs swift but the mechanisms leading to epigenetic and transcriptional reprogramming are poorly understood. The pediatric cancer neuroblastoma includes adrenergic (ADRN) and mesenchymal (MES) tumor cell types, which differ in phenotype, super-enhancers (SEs) and core regulatory circuitries. These cell types can spontaneously interconvert, but the mechanism remains largely unknown. Here, we unravel how a NOTCH3 intracellular domain reprogrammed the ADRN transcriptional landscape towards a MES state. A transcriptional feed-forward circuitry of NOTCH-family transcription factors amplifies the NOTCH signaling levels, explaining the swift transition between two semi-stable cellular states. This transition induces genome-wide remodeling of the H3K27ac landscape and a switch from ADRN SEs to MES SEs. Once established, the NOTCH feed-forward loop maintains the induced MES state. In vivo reprogramming of ADRN cells shows that MES and ADRN cells are equally oncogenic. Our results elucidate a swift transdifferentiation between two semi-stable epigenetic cellular states.
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المشرفين على المادة: 0 (NOTCH3 protein, human)
0 (Receptor, Notch3)
تواريخ الأحداث: Date Created: 20190406 Date Completed: 20190501 Latest Revision: 20210109
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6449373
DOI: 10.1038/s41467-019-09470-w
PMID: 30948783
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-019-09470-w