ArticleBlood2022
Editing TINF2 as a potential therapeutic approach to restore telomere length in dyskeratosis congenita.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.Nature communications · 2026Article
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Late-onset dyskeratosis congenita due to a TERC (n.269G > C) variant-first reported case from Indonesia: a case report.Journal of medical case reports · 2026Article
- Diagnosis and management of adult telomere biology disorders.Haematologica · 2026Review
- Dyskeratosis Congenita: Clinical Phenotype and Genetic Features in a Sibling Pair.Clinical, cosmetic and investigational dermatology · 2026Article
- Suspected parental gonadal/gonadosomatic mosaicism for a TINF2 mutation in two sisters with dyskeratosis congenita.Frontiers in genetics · 2026Article
- A rescue fanconi anemia humanized mouse model with endogenous FA mutation and high human hematopoietic stem cell chimerism.Molecular therapy. Methods & clinical development · 2025Article
- C-Terminal Extended Domain-Independent Telomere Maintenance: Modeling the Function of TIN2 Isoforms inInternational journal of molecular sciences · 2025Article
- Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients.Journal of clinical medicine · 2025Review
- Article
- UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.Stem cell research & therapy · 2024Article
- Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.Nature communications · 2024Article
- Clinical manifestations of telomere biology disorders in adults.Hematology. American Society of Hematology. Education Program · 2023Review
- Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.bioRxiv : the preprint server for biology · 2023Article
- Telomere-Associated Gene Signatures Correlate with Prognosis, Tumor Microenvironment, and Chemosensitivity in Breast Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the TINF2 gene, encoding the shelterin protein TIN2, cause telomere shortening and the inherited bone marrow (BM) failure syndrome dyskeratosis congenita (DC). A lack of suitable model systems limits the mechanistic understanding of telomere shortening in the stem cells and thus hinders the development of treatment options for BM failure. Here, we endogenously introduced TIN2-DC mutations in human embryonic stem cells (hESCs) and human hematopoietic stem and progenitor cells (HSPCs) to dissect the disease mechanism and identify a gene-editing strategy that rescued the disease phenotypes. The hESCs with the T284R disease mutation exhibited the short telomere phenotype observed in DC patients. Yet, telomeres in mutant hESCs did not trigger DNA damage responses at telomeres or show exacerbated telomere shortening when differentiated into telomerase-negative cells. Disruption of the mutant TINF2 allele by introducing a frameshift mutation in exon 2 restored telomere length in stem cells and the replicative potential of differentiated cells. Similarly, we introduced TIN2-DC disease variants in human HSPCs to assess the changes in telomere length and proliferative capacity. Lastly, we showed that editing at exon 2 of TINF2 that restored telomere length in hESCs could be generated in TINF2-DC patient HSPCs. Our study demonstrates a simple genetic intervention that rescues the TIN2-DC disease phenotype in stem cells and provides a versatile platform to assess the efficacy of potential therapeutic approaches in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.