{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:25:19Z","timestamp":1783445119032,"version":"3.54.6"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Chromatin architecture is highly dynamic, undergoing nanoscale rearrangements throughout the cell cycle and in response to environmental cues. In this study, we employed high-resolution stochastic optical reconstruction microscopy (STORM) to visualize chromatin organization and cellular plasticity at the nanoscale in two osteosarcoma cell lines, U2OS and MG63. To promote a tumor-suppressive bone microenvironment, we applied three biophysical modalities, namely mechanical vibration, electrical stimulation, and optical pulses, each previously linked to altered tumor behavior by reprogramming cells and generating induced tumor-suppressing (iTS) cells. These stimuli enlarged nuclear size and disrupted nuclear envelope integrity, as revealed by increased surface roughness. Critically, all three modalities transiently scattered nucleosome clusters, indicating chromatin decondensation as a hallmark of iTS cell generation. iTS cells exhibited elevated expression of histone demethylases lysine demethylase 3A (KDM3A) and lysine demethylase 4 (KDM4), accompanied by reduced levels of trimethylated histone H3 lysine 9 (H3K9me3). Consistently, pharmacological agents\u2014Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor\u2014induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment.<\/jats:p>","DOI":"10.3390\/cells15020113","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T14:32:38Z","timestamp":1767882758000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nucleosome Clustering as a Biomarker and Mechanistic Switch for Reprogramming Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8114-9808","authenticated-orcid":false,"given":"Zhaoyuan","family":"Xu","sequence":"first","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8889-4173","authenticated-orcid":false,"given":"Lidan","family":"You","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Materials Engineering, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-8959","authenticated-orcid":false,"given":"Hiroki","family":"Yokota","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University Indianapolis, Indianapolis, IN 46202, USA"},{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA"},{"name":"Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1158\/2159-8290.CD-24-0296","article-title":"The Epigenetic Hallmarks of Cancer","volume":"14","author":"Esteller","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, M., Sunkel, B.D., Ray, W.C., and Stanton, B.Z. 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