Reprogramming Fibroblasts of a Patient with Cockayne Syndrome Carrying Mutations in the  CSB/ERCC6  into iPSCs

P. I Sirotkina; Сироткина П. И; V. E Blokhin; Блохин В. Е; P. A Vasiliev; Васильев П. А; E. O Vorontsova; Воронцова Е. О; A. L Kungurtseva; Кунгурцева А. Л; A. V Vitebskaya; Витебская А. В; A. I Kalmykova; Калмыкова А. И; E. A Vorotelyak; Воротеляк Е. А; A. V Vasiliev; Васильев А. В; V. K Abdyev; Абдыев В. К

doi:10.7868/S3034626625060013

Reprogramming Fibroblasts of a Patient with Cockayne Syndrome Carrying Mutations in the CSB/ERCC6 into iPSCs

Authors: Sirotkina P.I¹, Blokhin V.E¹, Vasiliev P.A²^,3, Vorontsova E.O³, Kungurtseva A.L¹^,4, Vitebskaya A.V¹^,4, Kalmykova A.I¹, Vorotelyak E.A¹, Vasiliev A.V¹^,5, Abdyev V.K¹
Affiliations:
1. Koltzov Institute of Developmental Biology of Russian Academy of Sciences
2. Institute of Gene Biology, Russian Academy of Science institution
3. Research Centre for Medical Genetics
4. N.F. Filatov Clinical Institute of Children's Health, I.M. Sechenov First Moscow State Medical University
5. Department of Biology, Lomonosov Moscow State University
Issue: Vol 56, No 6 (2025)
Pages: 227-238
Section: Original study articles
URL: https://journals.rcsi.science/0475-1450/article/view/380373
DOI: https://doi.org/10.7868/S3034626625060013
ID: 380373

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Abstract

Cockayne syndrome (CS) is an autosomal recessive disorder. Mutations in one of two genes, CSA/ERCC8 and CSB/ERCC6, in the DNA repair mechanism are the cause of the hereditary progeroid disorder. In this report, we aimed to generate the iPSC line from fibroblasts, which carries the compound heterozygous mutations of c.2566C>T (p.Gln856Ter) and c.1821+1G>A in the CSB/ERCC6 gene. Dermal fibroblasts derived from a CS patient with compound heterozygous mutations in the CSB/ERCC6 gene were reprogrammed into an iPSC line (iPSC-CS-1), using episomal-based plasmid expressing OCT4, MYC, LIN28, shRNA against p53, SOX2, KLF4, and EBNA1. The IPSC-CS‑1 line demonstrated pluripotency characteristics by expressing pluripotency markers and differentiating into three germinal layers. The spontaneous differentiation of the iPSC-CS-1 line revealed reduced expression of the neuroectodermal marker OTX2.

Keywords

induced pluripotent stem cells, episomal reprogramming, Cockayne syndrome, progeroid syndrome, DNA damage, CSB/ERCC6

References

Abdyyev V.K., Sant D.W., Kiseleva E.V., Spangenberg V.E., Kolomiets O.L., Andrade N.S., et al. In vitro derived female hPGCLCs are unable to complete meiosis in embryoid bodies. Exp Cell Res. 2020 Dec 15; 397(2): 112358.
Gerdemann A., Behrens M., Günther G., Ghallab A., Hengstler J.G., Humpf H.U., et al. A simplified LC-MS-based method for sensitive analysis of DNA adducts utilizing accessible in vitro metabolism models. Arch Toxicol. 2025 Oct 8; 99(10): 4021–34.
Laugel V. Cockayne Syndrome. 2000 Dec 7 [Updated 2024 Feb 22]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1342/
Martins S., Hacheney I., Teichweyde N., Hildebrandt B., Krutmann J., Rossi A. Generation of an induced pluripotent stem cell line (IUFi001) from a Cockayne syndrome patient carrying a mutation in the ERCC6 gene. Stem Cell Res. 2021 Aug; 55: 102456.
Nance M.A., Berry S.A. Cockayne syndrome: review of 140 cases. Am J Med Genet. 1992 Jan 7; 42(1): 68–84.
Ozdirim E., Topçu M., Ozön A., Cila A. Cockayne syndrome: review of 25 cases. Pediatr Neurol. 1996 Nov; 15(4): 312–6.
Smith-Roe S.L., Hegan D.C., Glazer P.M., Buermeyer A.B. Mlh1-dependent suppression of specific mutations induced in vivo by the food-borne carcinogen 2-amino 1-methyl 6-phenylimidazo[4,5-b]pyridine (PhIP). Mutat Res. 2006 Feb; 594(1–2): 101–12.
Strzałka W., Zgłobicki P., Kowalska E., Bażant A., Dziga D., Banaś A.K. The Dark Side of UV–Induced DNA Lesion Repair. Genes (Basel). 2020 Dec 2; 11(12): 1450.
Zhang T., Akaike T., Sawa T. Redox Regulation of Xenobiotics by Reactive Sulfur and Supersulfide Species. Antioxid Redox Signal. 2024 Apr; 40(10–12): 679–90.

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