Academic Journal

Biophysical Regulation of Chromatin Architecture Instills a Mechanical Memory in Mesenchymal Stem Cells

التفاصيل البيبلوغرافية
العنوان: Biophysical Regulation of Chromatin Architecture Instills a Mechanical Memory in Mesenchymal Stem Cells
المؤلفون: Heo, Su-Jin, Thorpe, Stephen D., Driscoll, Tristan P., Duncan, Randall L., Lee, David A., Mauck, Robert L.
المساهمون: Su-Jin Heo, Stephen D. Thorpe, Tristan P. Driscoll, Randall L. Duncan, David A. Lee & Robert L. Mauck, Duncan, Randall L.
المصدر: Scientific Reports ; http://www.nature.com/srep/
بيانات النشر: Nature Publishing Group
سنة النشر: 2015
المجموعة: The University of Delaware Library Institutional Repository
الوصف: Publisher's PDF. ; Mechanical cues direct the lineage commitment of mesenchymal stem cells (MSCs). In this study, we identified the operative molecular mechanisms through which dynamic tensile loading (DL) regulates changes in chromatin organization and nuclear mechanics in MSCs. Our data show that, in the absence of exogenous differentiation factors, short term DL elicits a rapid increase in chromatin condensation, mediated by acto-myosin based cellular contractility and the activity of the histone-lysine N-methyltransferase EZH2. The resulting change in chromatin condensation stiffened the MSC nucleus, making it less deformable when stretch was applied to the cell. We also identified stretch induced ATP release and purinergic calcium signaling as a central mediator of this chromatin condensation process. Further, we showed that DL, through differential stabilization of the condensed chromatin state, established a ‘mechanical memory’ in these cells. That is, increasing strain levels and number of loading events led to a greater degree of chromatin condensation that persisted for longer periods of time after the cessation of loading. These data indicate that, with mechanical perturbation, MSCs develop a mechanical memory encoded in structural changes in the nucleus which may sensitize them to future mechanical loading events and define the trajectory and persistence of their lineage specification. ; University of Delaware. Department of Biological Sciences.
نوع الوثيقة: article in journal/newspaper
وصف الملف: text/plain; application/pdf
اللغة: English
تدمد: 2045-2322
Relation: Heo, S.-J. et al. Biophysical Regulation of Chromatin Architecture Instills a Mechanical Memory in Mesenchymal Stem Cells. Sci. Rep. 5, 16895; doi:10.1038/srep16895 (2015).; http://udspace.udel.edu/handle/19716/17315
DOI: 10.1038/srep16895
الاتاحة: http://udspace.udel.edu/handle/19716/17315
https://doi.org/10.1038/srep16895
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
رقم الانضمام: edsbas.100B5D24
قاعدة البيانات: BASE
الوصف
تدمد:20452322
DOI:10.1038/srep16895