{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:03:29Z","timestamp":1789621409099,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RESEARCH\u2014CREATE\u2014INNOVATE","award":["T1EDK-000128"],"award-info":[{"award-number":["T1EDK-000128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Osteoarthritis (OA) is strongly associated with mitochondrial dysfunction, oxidative stress, and the accumulation of mitochondrial DNA (mtDNA) alterations in several joint-associated cell types, including chondrocytes, synoviocytes, and mesenchymal stromal cells (MSCs). These alterations contribute to impaired cellular homeostasis and reduced regenerative potential. In this study, we systematically characterized mtDNA heteroplasmy and variant distribution across bone marrow MSCs, induced pluripotent stem cells (iPSCs) and induced MSCs (iMSCs) derived from OA patients and healthy donors. Methods: Ultra-deep mitochondrial genome sequencing was integrated with transcriptomic and miRNome analyses to investigate mitochondrial remodeling during cellular reprogramming, encompassing changes in mtDNA heteroplasmy, variant distribution, mtDNA copy number and associated transcriptomic adaptations of nuclear-encoded mitochondrial pathways. Results: OA-derived MSCs exhibited a markedly increased heteroplasmic burden, followed by decrease in mtDNA copy number and accumulation of non-synonymous variants, particularly within OXPHOS-related genes, including MT-ND1-5, MT-ATP8, MT-CO1, and MT-RNR1\/2. Reprogramming into iPSCs and subsequent differentiation into iMSCs were associated with an increase in mtDNA copy number and a progressive reduction in heteroplasmic variants predicted to have pathogenic potential, including m.7913C&gt;T and m.7821G&gt;A, as well as substantial reduction in heteroplasmic variant burden within several mitochondrial genes, suggesting mitochondrial genome remodeling during cellular reprogramming. Multiomic analysis further revealed coordinated deregulation of mitochondrial-associated nuclear genes and ceRNA regulatory networks involving lncRNAs MEG3 and SNHG14, along with multiple mitochondria-related miRNAs. These findings suggest post-transcriptional regulations associated with mitochondrial adaptation in iMSCs Conclusion: Collectively, our findings suggest that cellular reprogramming is associated with mitochondrial genomic reorganization in the donor-matched cell populations examined. These exploratory observations support the utility of iMSCs as a relevant model for studying OA-associated mitochondrial alterations and as a potential tool for regenerative approaches in OA.<\/jats:p>","DOI":"10.3390\/genes17091101","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:39:24Z","timestamp":1789137564000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the Mitochondrial Genome Landscape in MSCs, iPSCs and iMSCs from Osteoarthritis Patients and Healthy Donors"],"prefix":"10.3390","volume":"17","author":[{"given":"Vasileios","family":"Konteles","sequence":"first","affiliation":[{"name":"Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-2922","authenticated-orcid":false,"given":"Maria","family":"Tzetis","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenios","family":"Goussetis","sequence":"additional","affiliation":[{"name":"Stem Cell Transplant Unit, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostantinos","family":"Malizos","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aspasia","family":"Tsezou","sequence":"additional","affiliation":[{"name":"Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrrheum.2016.65","article-title":"Ageing and the Pathogenesis of Osteoarthritis","volume":"12","author":"Loeser","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/art.10837","article-title":"Mitochondrial Respiratory Activity Is Altered in Osteoarthritic Human Articular Chondrocytes","volume":"48","author":"Maneiro","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41413-025-00460-x","article-title":"The Impact of Mitochondrial Dysfunction on Osteoarthritis Cartilage: Current Insights and Emerging Mitochondria-Targeted Therapies","volume":"13","author":"Tan","year":"2025","journal-title":"Bone Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11643","DOI":"10.1038\/s41598-020-68566-2","article-title":"Mitochondrial Dysfunction Impairs Osteogenesis, Increases Osteoclast Activity, and Accelerates Age Related Bone Loss","volume":"10","author":"Dobson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrg3966","article-title":"The Dynamics of Mitochondrial DNA Heteroplasmy: Implications for Human Health and Disease","volume":"16","author":"Stewart","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41584-018-0001-0","article-title":"Mitochondrial DNA Variation and the Pathogenesis of Osteoarthritis Phenotypes","volume":"14","author":"Blanco","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/ard-2022-223570","article-title":"A Meta-Analysis and a Functional Study Support the Influence of MtDNA Variant m.16519C on the Risk of Rapid Progression of Knee Osteoarthritis","volume":"82","author":"Calamia","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3892\/ijmm.2025.5559","article-title":"Understanding the Impact of Mitochondrial DNA Mutations on Aging and Carcinogenesis (Review)","volume":"56","author":"Kobayashi","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/s41419-020-03289-w","article-title":"Adult Mesenchymal Stem Cell Ageing Interplays with Depressed Mitochondrial Ndufs6","volume":"11","author":"Zhang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.stem.2016.02.005","article-title":"Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human Ipscs","volume":"18","author":"Kang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e55678","DOI":"10.15252\/embr.202255678","article-title":"Modeling Mitochondrial DNA Diseases: From Base Editing to Pluripotent Stem-cell-derived Organoids","volume":"24","author":"Tolle","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20989","DOI":"10.1038\/s41598-024-71822-4","article-title":"Variant Load of Mitochondrial DNA in Single Human Mesenchymal Stem Cells","volume":"14","author":"Hipps","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1038\/s41467-021-25482-x","article-title":"Cell Reprogramming Shapes the Mitochondrial DNA Landscape","volume":"12","author":"Wei","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/s12276-025-01476-3","article-title":"Changes in Mitochondrial Thymidine Metabolism and MtDNA Copy Number during Induced Pluripotency","volume":"57","author":"Kim","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Salti, A., Etemad, S., Cubero, M.S., Albertini, E., Kovacs-Szalka, B., Holzknecht, M., Cappuccio, E., Cavinato, M., Edenhofer, F., and D\u00fcrr, P.J. (2021). High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-Ko Mouse Embryonic Fibroblasts. Cells, 10.","DOI":"10.3390\/cells10082040"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1038\/s41598-021-84071-6","article-title":"Characterization of Mitochondrial Health from Human Peripheral Blood Mononuclear Cells to Cerebral Organoids Derived from Induced Pluripotent Stem Cells","volume":"11","author":"Duong","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8073721","DOI":"10.1155\/2017\/8073721","article-title":"Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer","volume":"2017","author":"Prieto","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.stem.2016.04.015","article-title":"Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program","volume":"19","author":"Khacho","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tcb.2020.12.009","article-title":"Mitochondrial DNA Dynamics in Reprogramming to Pluripotency","volume":"31","author":"Sercel","year":"2021","journal-title":"Trends Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.stemcr.2024.01.009","article-title":"Mitochondrial DNA Integrity and Metabolome Profile Are Preserved in the Human Induced Pluripotent Stem Cell Reference Line KOLF2.1J","volume":"19","author":"Dobner","year":"2024","journal-title":"Stem Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"689","DOI":"10.5483\/BMBRep.2019.52.12.045","article-title":"Mitochondrial Genome Mutations in Mesenchymal Stem Cells Derived from Human Dental Induced Pluripotent Stem Cells","volume":"52","author":"Park","year":"2019","journal-title":"BMB Rep."},{"key":"ref_22","first-page":"1415","article-title":"Proliferative and Chondrogenic Potential of Mesenchymal Stromal Cells from Pluripotent and Bone Marrow Cells","volume":"35","author":"Sfougataki","year":"2020","journal-title":"Histol. Histopathol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Konteles, V., Papathanasiou, I., Tzetis, M., Goussetis, E., Trachana, V., Mourmoura, E., Balis, C., Malizos, K., and Tsezou, A. (2023). Integration of Transcriptome and MicroRNA Profile Analysis of IMSCs Defines Their Rejuvenated State and Conveys Them into a Novel Resource for Cell Therapy in Osteoarthritis. Cells, 12.","DOI":"10.3390\/cells12131756"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1093\/hmg\/ddac059","article-title":"Mitochondrial DNA Variants Segregate during Human Preimplantation Development into Genetically Different Cell Lineages That Are Maintained Postnatally","volume":"31","author":"Mertens","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/s41419-019-2018-y","article-title":"MLH1 Deficiency Leads to Deregulated Mitochondrial Metabolism","volume":"10","author":"Rashid","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/s41598-024-52373-0","article-title":"Nuclear and Mitochondrial Genetic Variants Associated with Mitochondrial DNA Copy Number","volume":"14","author":"Koller","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D1541","DOI":"10.1093\/nar\/gkaa1011","article-title":"MitoCarta3.0: An Updated Mitochondrial Proteome Now with Sub-Organelle Localization and Pathway Annotations","volume":"49","author":"Rath","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.redox.2014.07.005","article-title":"Mitochondrial Stress Signaling in Longevity: A New Role for Mitochondrial Function in Aging","volume":"2","author":"Hill","year":"2014","journal-title":"Redox Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Annesley, S.J., and Fisher, P.R. (2019). Mitochondria in Health and Disease. Cells, 8.","DOI":"10.3390\/cells8070680"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1002\/1878-0261.13291","article-title":"Mitochondrial DNA Mutations in Ageing and Cancer","volume":"16","author":"Smith","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhong, G., Madry, H., and Cucchiarini, M. (2022). Mitochondrial Genome Editing to Treat Human Osteoarthritis\u2014A Narrative Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031467"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13321","DOI":"10.1111\/acel.13321","article-title":"Age-Associated Mitochondrial Complex I Deficiency Is Linked to Increased Stem Cell Proliferation Rates in the Mouse Colon","volume":"20","author":"Stamp","year":"2021","journal-title":"Aging Cell"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jasra, I.T., Cuesta-Gomez, N., Verhoeff, K., Marfil-Garza, B.A., Dadheech, N., and Shapiro, A.M.J. (2023). Mitochondrial Regulation in Human Pluripotent Stem Cells during Reprogramming and \u03b2 Cell Differentiation. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1236472"},{"key":"ref_35","first-page":"3308","article-title":"Effect of Chondrocyte Mitochondrial Dysfunction on Cartilage Degeneration: A Possible Pathway for Osteoarthritis Pathology at the Subcellular Level","volume":"20","author":"Liu","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kuznetsov, A.V., Margreiter, R., Ausserlechner, M.J., and Hagenbuchner, J. (2022). The Complex Interplay between Mitochondria, ROS and Entire Cellular Metabolism. Antioxidants, 11.","DOI":"10.3390\/antiox11101995"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41413-024-00344-6","article-title":"PDZK1 Protects against Mechanical Overload-Induced Chondrocyte Senescence and Osteoarthritis by Targeting Mitochondrial Function","volume":"12","author":"Shao","year":"2024","journal-title":"Bone Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6520","DOI":"10.1126\/science.aau6520","article-title":"Germline Selection Shapes Human Mitochondrial DNA Diversity","volume":"364","author":"Wei","year":"2019","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112590","DOI":"10.1016\/j.isci.2025.112590","article-title":"Deleterious Mitochondrial Heteroplasmies Exhibit Increased Longitudinal Change in Variant Allele Fraction","volume":"28","author":"Kuiper","year":"2025","journal-title":"iScience"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41586-024-07332-0","article-title":"Single-Cell Analysis Reveals Context-Dependent, Cell-Level Selection of MtDNA","volume":"629","author":"Kotrys","year":"2024","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/dgd.12420","article-title":"Mitochondrial DNA Heteroplasmy and Purifying Selection in the Mammalian Female Germ Line","volume":"60","author":"Burr","year":"2018","journal-title":"Dev. Growth Differ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1.23.1","DOI":"10.1002\/0471250953.bi0123s44","article-title":"MtDNA Variation and Analysis Using Mitomap and Mitomaster","volume":"44","author":"Lott","year":"2013","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/s41586-023-06426-5","article-title":"Nuclear Genetic Control of MtDNA Copy Number and Heteroplasmy in Humans","volume":"620","author":"Gupta","year":"2023","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"EMBR201949612","DOI":"10.15252\/embr.201949612","article-title":"Mitochondrial DNA Heteroplasmy in Disease and Targeted Nuclease-based Therapeutic Approaches","volume":"21","author":"Nissanka","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cmet.2011.06.011","article-title":"Somatic Oxidative Bioenergetics Transitions into Pluripotency-Dependent Glycolysis to Facilitate Nuclear Reprogramming","volume":"14","author":"Folmes","year":"2011","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1016\/j.devcel.2024.04.012","article-title":"Cox7a1 Controls Skeletal Muscle Physiology and Heart Regeneration through Complex IV Dimerization","volume":"59","author":"Arora","year":"2024","journal-title":"Dev. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wu, Q., Bai, S., Song, L., Han, L., and Wang, P. (2026). COX7A1-Mediated Mitochondrial Dysfunction Can Induce Ferroptosis in Endometrial Cancer Cells. PLoS ONE, 21.","DOI":"10.1371\/journal.pone.0342333"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41419-022-05430-3","article-title":"COX7A1 Enhances the Sensitivity of Human NSCLC Cells to Cystine Deprivation-Induced Ferroptosis via Regulating Mitochondrial Metabolism","volume":"13","author":"Feng","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mallajosyula, J.K., Kaur, D., Chinta, S.J., Rajagopalan, S., Rane, A., Nicholls, D.G., Di Monte, D.A., Macarthur, H., and Andersen, J.K. (2008). MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson\u2019s Pathology. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001616"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.33696\/Signaling.6.134","article-title":"Monoamine Oxidase B in Astrocytic GABA Synthesis: A Central Mechanism in Neurodegeneration and Neuroinflammation","volume":"6","author":"Naffaa","year":"2025","journal-title":"J. Cell. Signal."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature12985","article-title":"Mitochondrial Form and Function","volume":"505","author":"Friedman","year":"2014","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/ng.2325","article-title":"Mutations in the Phospholipid Remodeling Gene SERAC1 Impair Mitochondrial Function and Intracellular Cholesterol Trafficking and Cause Dystonia and Deafness","volume":"44","author":"Wortmann","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1261\/rna.038521.113","article-title":"GPAT2, a Mitochondrial Outer Membrane Protein, in PiRNA Biogenesis in Germline Stem Cells","volume":"19","author":"Shiromoto","year":"2013","journal-title":"RNA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.7150\/jca.55495","article-title":"LncRNA SNHG14 Promotes Cell Proliferation and Invasion in Colorectal Cancer through Modulating MiR-519b-3p\/DDX5 Axis","volume":"12","author":"Wang","year":"2021","journal-title":"J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"De Giusti, C.J., Roman, B., and Das, S. (2018). The Influence of MicroRNAs on Mitochondrial Calcium. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01291"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Piergentili, R., and Sechi, S. (2024). Non-Coding RNAs of Mitochondrial Origin: Roles in Cell Division and Implications in Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137498"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1101\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:27:33Z","timestamp":1789619253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091101"],"URL":"https:\/\/doi.org\/10.3390\/genes17091101","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}