{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:57:16Z","timestamp":1767830236537,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Coats plus (CP) syndrome is an inherited autosomal recessive condition that results from mutations in the conserved telomere maintenance component 1 gene (CTC1). The CTC1 protein functions as a part of the CST protein complex, a protein heterotrimer consisting of CTC1\u2013STN1\u2013TEN1 which promotes telomere DNA synthesis and inhibits telomerase-mediated telomere elongation. However, it is unclear how CTC1 mutations may have an effect on telomere structure and function. For that purpose, we established the very first induced pluripotent stem cell lines (iPSCs) from a compound heterozygous patient with CP carrying deleterious mutations in both alleles of CTC1. Telomere dysfunction and chromosomal instability were assessed in both circulating lymphocytes and iPSCs from the patient and from healthy controls of similar age. The circulating lymphocytes and iPSCs from the CP patient were characterized by their higher telomere length heterogeneity and telomere aberrations compared to those in control cells from healthy donors. Moreover, in contrast to iPSCs from healthy controls, the high levels of telomerase were associated with activation of the alternative lengthening of telomere (ALT) pathway in CP-iPSCs. This was accompanied by inappropriate activation of the DNA repair proteins \u03b3H2AX, 53BP1, and ATM, as well as with accumulation of DNA damage, micronuclei, and anaphase bridges. CP-iPSCs presented features of cellular senescence and increased radiation sensitivity. Clonal dicentric chromosomes were identified only in CP-iPSCs after exposure to radiation, thus mirroring the role of telomere dysfunction in their formation. These data demonstrate that iPSCs derived from CP patients can be used as a model system for molecular studies of the CP syndrome and underscores the complexity of telomere dysfunction associated with the defect of DNA repair machinery in the CP syndrome.<\/jats:p>","DOI":"10.3390\/genes13081395","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"1395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Patient-Derived iPSCs Reveal Evidence of Telomere Instability and DNA Repair Deficiency in Coats Plus Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Noufissa","family":"Oudrhiri","sequence":"first","affiliation":[{"name":"Inserm UMR_S_1310, 94805 Villejuif, France"},{"name":"APHP Paris Saclay Service Onco-Hematology and Cytogenetics, Paul-Brousse, 94805 Villejuif, France"},{"name":"INGESTEM National iPSC Infrastructure, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0639-4760","authenticated-orcid":false,"given":"Radhia","family":"M\u2019kacher","sequence":"additional","affiliation":[{"name":"Inserm UMR_S_1310, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-8341","authenticated-orcid":false,"given":"Diana","family":"Chaker","sequence":"additional","affiliation":[{"name":"INGESTEM National iPSC Infrastructure, 94805 Villejuif, France"},{"name":"Centre for iPSC Therapies (CITHERA) INSERM UMS 45, Genopole, 91000 Evry-Courcouronnes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1742-8631","authenticated-orcid":false,"given":"Bruno","family":"Colicchio","sequence":"additional","affiliation":[{"name":"IRIMAS, Institut de Recherche en Informatique, Math\u00e9matiques, Automatique et Signal, Universit\u00e9 de Haute-Alsace, 68070 Mulhouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Borie","sequence":"additional","affiliation":[{"name":"Inserm UMR_S_1310, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-0770","authenticated-orcid":false,"given":"Eric","family":"Jeandidier","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique, Groupe Hospitalier de la R\u00e9gion de Mulhouse Sud-Alsace, 68070 Mulhouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Dieterlen","sequence":"additional","affiliation":[{"name":"IRIMAS, Institut de Recherche en Informatique, Math\u00e9matiques, Automatique et Signal, Universit\u00e9 de Haute-Alsace, 68070 Mulhouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Griscelli","sequence":"additional","affiliation":[{"name":"INGESTEM National iPSC Infrastructure, 94805 Villejuif, France"},{"name":"Centre for iPSC Therapies (CITHERA) INSERM UMS 45, Genopole, 91000 Evry-Courcouronnes, France"},{"name":"D\u00e9partement de Biologie M\u00e9dicale et Pathologie M\u00e9dicales, Service de Microbiologie, Gustave Roussy Cancer Campus, 94805 Villejuif, France"},{"name":"Facult\u00e9 des Sciences Pharmaceutiques et Biologiques, Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelise","family":"Bennaceur-Griscelli","sequence":"additional","affiliation":[{"name":"Inserm UMR_S_1310, 94805 Villejuif, France"},{"name":"APHP Paris Saclay Service Onco-Hematology and Cytogenetics, Paul-Brousse, 94805 Villejuif, France"},{"name":"INGESTEM National iPSC Infrastructure, 94805 Villejuif, France"},{"name":"Centre for iPSC Therapies (CITHERA) INSERM UMS 45, Genopole, 91000 Evry-Courcouronnes, France"},{"name":"APHP-Paris Saclay Service d\u2019H\u00e9matologie-Bicetre, 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-0137","authenticated-orcid":false,"given":"Ali G.","family":"Turhan","sequence":"additional","affiliation":[{"name":"Inserm UMR_S_1310, 94805 Villejuif, France"},{"name":"APHP Paris Saclay Service Onco-Hematology and Cytogenetics, Paul-Brousse, 94805 Villejuif, France"},{"name":"INGESTEM National iPSC Infrastructure, 94805 Villejuif, France"},{"name":"Centre for iPSC Therapies (CITHERA) INSERM UMS 45, Genopole, 91000 Evry-Courcouronnes, France"},{"name":"APHP-Paris Saclay Service d\u2019H\u00e9matologie-Bicetre, 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.12688\/f1000research.14068.1","article-title":"Beginning at the ends: Telomeres and human disease","volume":"7","author":"Savage","year":"2018","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nrm.2016.43","article-title":"Stop pulling my strings-what telomeres taught us about the DNA damage response","volume":"17","author":"Sfeir","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev.genet.41.110306.130350","article-title":"How shelterin protects mammalian telomeres","volume":"42","author":"Palm","year":"2008","journal-title":"Annu. Rev. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.gde.2020.01.005","article-title":"Telomere instability initiates and then boosts carcinogenesis by the butterfly effect","volume":"60","author":"Herate","year":"2020","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1101\/gad.294108.116","article-title":"The DDR at telomeres lacking intact shelterin does not require substantial chromatin decompaction","volume":"31","author":"Timashev","year":"2017","journal-title":"Genes Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/ng.1084","article-title":"Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus","volume":"44","author":"Anderson","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.neurol.2015.01.566","article-title":"Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene","volume":"171","author":"Bisserbe","year":"2015","journal-title":"Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3928\/01913913-20190716-01","article-title":"Coats Disease: Clinical Features and Outcomes by Age Category in 351 Cases","volume":"56","author":"Dalvin","year":"2019","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1101\/gad.222893.113","article-title":"Molecular basis of telomere syndrome caused by CTC1 mutations","volume":"27","author":"Chen","year":"2013","journal-title":"Genes Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1111\/acel.12139","article-title":"Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus","volume":"12","author":"Gu","year":"2013","journal-title":"Aging Cell"},{"key":"ref_11","first-page":"3981","article-title":"Pathogenic CTC1 mutations cause global genome instabilities under replication stress","volume":"46","author":"Rechavi","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1084\/jem.20151618","article-title":"Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects","volume":"213","author":"Simon","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41419-017-0141-1","article-title":"iPSC modeling of severe aplastic anemia reveals impaired differentiation and telomere shortening in blood progenitors","volume":"9","author":"Xu","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.scr.2017.09.003","article-title":"Generation of induced pluripotent stem cell (iPSC) line from a patient with triple negative breast cancer with hereditary exon 17 deletion of BRCA1 gene","volume":"24","author":"Griscelli","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ijrobp.2007.01.050","article-title":"Telomere shortening and associated chromosomal instability in peripheral blood lymphocytes of patients with Hodgkin\u2019s lymphoma prior to any treatment are predictive of second cancers","volume":"68","author":"Girinsky","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mrfmmm.2014.09.007","article-title":"New tool for biological dosimetry: Reevaluation and automation of the gold standard method following telomere and centromere staining","volume":"770","author":"Maalouf","year":"2014","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"M\u2019Kacher, R., Cuceu, C., Al Jawhari, M., Morat, L., Frenzel, M., Shim, G., Lenain, A., Hempel, W.M., Junker, S., and Girinsky, T. (2018). The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes. Cancers, 10.","DOI":"10.3390\/cancers10060169"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1038\/s41598-017-03198-7","article-title":"Transmission of Induced Chromosomal Aberrations through Successive Mitotic Divisions in Human Lymphocytes after In Vitro and In Vivo Radiation","volume":"7","author":"Kaddour","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.mrfmmm.2011.04.008","article-title":"Telomere dysfunction and chromosome instability","volume":"730","author":"Murnane","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cell.2009.06.021","article-title":"Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication","volume":"138","author":"Sfeir","year":"2009","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1128\/MCB.00009-09","article-title":"Arginine methylation regulates telomere length and stability","volume":"29","author":"Mitchell","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1002\/jat.3425","article-title":"Genotoxic risk of ethyl-paraben could be related to telomere shortening","volume":"37","author":"Finot","year":"2017","journal-title":"J. Appl. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"503143","DOI":"10.1016\/j.mrgentox.2020.503143","article-title":"A new tool for genotoxic risk assessment: Reevaluation of the cytokinesis-block micronucleus assay using semi-automated scoring following telomere and centromere staining","volume":"850-851","author":"Zaguia","year":"2020","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cuceu, C., Hempel, W.M., Sabatier, L., Bosq, J., Carde, P., and M\u2019Kacher, R. (2018). Chromosomal Instability in Hodgkin Lymphoma: An In-Depth Review and Perspectives. Cancers, 10.","DOI":"10.3390\/cancers10040091"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"M\u2019Kacher, R., Colicchio, B., Borie, C., Junker, S., Marquet, V., Heidingsfelder, L., Soehnlen, K., Najar, W., Hempel, W.M., and Oudrhiri, N. (2020). Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility. Genes, 11.","DOI":"10.3390\/genes11050475"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ramlee, M.K., Wang, J., Toh, W.X., and Li, S. (2016). Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene. Genes, 7.","DOI":"10.3390\/genes7080050"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1038\/nprot.2007.418","article-title":"Induction of pluripotent stem cells from fibroblast cultures","volume":"2","author":"Takahashi","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15726","DOI":"10.1073\/pnas.0907689106","article-title":"Probing PML body function in ALT cells reveals spatiotemporal requirements for telomere recombination","volume":"106","author":"Draskovic","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7072","DOI":"10.1158\/0008-5472.CAN-07-1556","article-title":"DNA damage induces alternative lengthening of telomeres (ALT) associated promyelocytic leukemia bodies that preferentially associate with linear telomeric DNA","volume":"67","author":"Fasching","year":"2007","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17312","DOI":"10.1073\/pnas.0407162101","article-title":"Accelerated telomere shortening in response to life stress","volume":"101","author":"Epel","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/ncomms1708","article-title":"Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence","volume":"3","author":"Hewitt","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/cge.13526","article-title":"Telomeropathies: Etiology, diagnosis, treatment and follow-up. Ethical and legal considerations","volume":"96","author":"Armando","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ceb.2017.12.001","article-title":"Telomeres and aging","volume":"52","author":"Shay","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ajhg.2012.02.002","article-title":"Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts","volume":"90","author":"Polvi","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1002\/mgg3.495","article-title":"CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures","volume":"6","author":"Sargolzaeiaval","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/pbc.24193","article-title":"CTC1 Mutations in a patient with dyskeratosis congenita","volume":"59","author":"Keller","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1101\/gad.276873.115","article-title":"A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus","volume":"30","author":"Takai","year":"2016","journal-title":"Genes Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3324\/haematol.2012.071068","article-title":"Mutations in the telomere capping complex in bone marrow failure and related syndromes","volume":"98","author":"Walne","year":"2013","journal-title":"Haematologica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.biosystems.2017.07.006","article-title":"The lamin code","volume":"164","author":"Maraldi","year":"2018","journal-title":"Biosystems"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9886","DOI":"10.1093\/nar\/gkab761","article-title":"Increase in lamin B1 promotes telomere instability by disrupting the shelterin complex in human cells","volume":"49","author":"Pennarun","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/j.cell.2015.11.054","article-title":"Chromothripsis and Kataegis Induced by Telomere Crisis","volume":"163","author":"Maciejowski","year":"2015","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4161\/epi.6.1.13390","article-title":"Reprogramming of telomeric regions during the generation of human induced pluripotent stem cells and subsequent differentiation into fibroblast-like derivatives","volume":"6","author":"Yehezkel","year":"2011","journal-title":"Epigenetics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.stem.2008.12.010","article-title":"Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells","volume":"4","author":"Marion","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1172\/JCI67146","article-title":"Defective telomere elongation and hematopoiesis from telomerase-mutant aplastic anemia iPSCs","volume":"123","author":"Winkler","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cuceu, C., Colicchio, B., Jeandidier, E., Junker, S., Plassa, F., Shim, G., Mika, J., Frenzel, M., AL Jawhari, M., and Hempel, W.M. (2018). Independent Mechanisms Lead to Genomic Instability in Hodgkin Lymphoma: Microsatellite or Chromosomal Instability. Cancers, 10.","DOI":"10.3390\/cancers10070233"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/08880010390243086","article-title":"Sensitivity to radiation and alkylating agent of peripheral lymphocytes and fibroblasts in a Hoyeraal-Hreidarsson syndrome patient","volume":"20","author":"Laithier","year":"2003","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbmt.2016.01.026","article-title":"A Reduced-Intensity Conditioning Regimen for Patients with Dyskeratosis Congenita Undergoing Hematopoietic Stem Cell Transplantation","volume":"22","author":"Nelson","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pereboeva, L., Westin, E., Patel, T., Flaniken, I., Lamb, L., Klingelhutz, A., and Goldman, F. (2013). DNA damage responses and oxidative stress in dyskeratosis congenita. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076473"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1158\/0008-5472.CAN-12-3125","article-title":"Telomere length and telomerase activity impact the UV sensitivity syndrome xeroderma pigmentosum C","volume":"73","author":"Stout","year":"2013","journal-title":"Cancer Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:04:45Z","timestamp":1760141085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,5]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["genes13081395"],"URL":"https:\/\/doi.org\/10.3390\/genes13081395","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,5]]}}}