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Periodontitis is a typical case characterized by decreased ECM stiffness within diseased periodontal tissues as well as with irreversible loss of osteogenesis capacity of periodontal tissue-derived human periodontal tissue-derived MSCs (hMSCs) even returning back to a physiological mechanical microenvironment. We hypothesized that the hMSCs extendedly residing in the soft ECM of diseased periodontal tissues may memorize the mechanical information and have further effect on ultimate cell fate besides the current mechanical microenvironment. Using a soft priming and subsequent stiff culture system based on collagen-modified polydimethylsiloxane substrates, we were able to discover that extended preconditioning on soft matrices (e.g., 7\u2009days of exposure) led to approximately one-third decrease in cell spreading, two-third decrease in osteogenic markers (e.g., RUNX2 and OPN) of hMSCs, and one-thirteenth decrease in the production of mineralized nodules. The significant loss of osteogenic ability may attribute to the long-term residing of hMSCs in diseased periodontal tissue featured with reduced stiffness. This is associated with the regulation of transcriptional activity through alterations of subcellular localization of yes-associated protein and nuclear feature-mediated chromatin organization. Collectively, we reconstructed phenomena of irreversible loss of hMSC osteogenesis capacity in diseased periodontal tissues in our system and revealed the critical effect of preconditioning duration on soft matrices as well as the potential mechanisms in determining ultimate hMSC fate.<\/jats:p>","DOI":"10.1063\/5.0124424","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T20:00:52Z","timestamp":1677096052000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Extended preconditioning on soft matrices directs human mesenchymal stem cell fate via YAP transcriptional activity and chromatin organization"],"prefix":"10.1063","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-0559","authenticated-orcid":false,"given":"Yufei","family":"Ma","sequence":"first","affiliation":[{"name":"Bioinspired Engineering and Biomechanics Center (BEBC), The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University 1 , Xi'an 710049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bioinspired Engineering and Biomechanics Center (BEBC), The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University 1 , Xi'an 710049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxin","family":"Tang","sequence":"additional","affiliation":[{"name":"Bioinspired Engineering and Biomechanics Center (BEBC), The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University 1 , Xi'an 710049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xue","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro\/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-End Equipment, Xi'an Jiaotong University 2 , Xi'an 710049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioinspired Engineering and Biomechanics Center (BEBC), The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University 1 , Xi'an 710049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-7376","authenticated-orcid":false,"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro\/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-End Equipment, Xi'an Jiaotong University 2 , Xi'an 710049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"issue":"5411","key":"2023081023290486200_c1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","year":"1999","journal-title":"Science"},{"issue":"6893","key":"2023081023290486200_c2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nature00870","article-title":"Pluripotency of mesenchymal stem cells derived from adult marrow","volume":"418","year":"2002","journal-title":"Nature"},{"issue":"7","key":"2023081023290486200_c3","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/nbt987","article-title":"A role for chemistry in stem cell biology","volume":"22","year":"2004","journal-title":"Nat. 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