ArticleThe Journal of clinical investigation2013
Defective telomere elongation and hematopoiesis from telomerase-mutant aplastic anemia iPSCs.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Danazol Treatment for Telomere Diseases.The New England journal of medicine · 2016Trial
- Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia.Acta haematologica · 2016Trial
- Bone marrow skeletal stem/progenitor cell defects in dyskeratosis congenita and telomere biology disorders.Blood · 2015Trial
- Telomerase is essential for cardiac differentiation and sustained metabolism of human cardiomyocytes.Cellular and molecular life sciences : CMLS · 2024Article
- TERC haploid cell reprogramming: a novel therapeutic strategy for aplastic anemia.Molecular medicine (Cambridge, Mass.) · 2023Review
- Article
- Defective hematopoietic differentiation of immune aplastic anemia patient-derived iPSCs.Cell death & disease · 2022Article
- Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue.Blood · 2022Article
- Hematopoiesis under telomere attrition at the single-cell resolution.Nature communications · 2021Article
- Differentiation of human induced pluripotent stem cells into erythroid cells.Stem cell research & therapy · 2020Review
- Telomere Dysfunction Activates p53 and Represses HNF4α Expression Leading to Impaired Human Hepatocyte Development and Function.Hepatology (Baltimore, Md.) · 2020Article
- Chemical inhibition of PAPD5/7 rescues telomerase function and hematopoiesis in dyskeratosis congenita.Blood advances · 2020Article
- Acquired Aplastic Anemia as a Clonal Disorder of Hematopoietic Stem Cells.Stem cell reviews and reports · 2020Review
- Telomere dynamics and hematopoietic differentiation of human DKC1-mutant induced pluripotent stem cells.Stem cell research · 2019Article
- Modeling blood diseases with human induced pluripotent stem cells.Disease models & mechanisms · 2019Review
- Article
- iPSC modeling of severe aplastic anemia reveals impaired differentiation and telomere shortening in blood progenitors.Cell death & disease · 2018Article
- HeterozygousBlood advances · 2018Article
- Telomerase enzyme deficiency promotes metabolic dysfunction in murine hepatocytes upon dietary stress.Liver international : official journal of the International Association for the Study of the Liver · 2018Article
- The Telomerase Complex Directly Controls Hematopoietic Stem Cell Differentiation and Senescence in an Induced Pluripotent Stem Cell Model of Telomeropathy.Frontiers in genetics · 2018Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Critically short telomeres activate p53-mediated apoptosis, resulting in organ failure and leading to malignant transformation. Mutations in genes responsible for telomere maintenance are linked to a number of human diseases. We derived induced pluripotent stem cells (iPSCs) from 4 patients with aplastic anemia or hypocellular bone marrow carrying heterozygous mutations in the telomerase reverse transcriptase (TERT) or the telomerase RNA component (TERC) telomerase genes. Both mutant and control iPSCs upregulated TERT and TERC expression compared with parental fibroblasts, but mutant iPSCs elongated telomeres at a lower rate compared with healthy iPSCs, and the deficit correlated with the mutations' impact on telomerase activity. There was no evidence for alternative lengthening of telomere (ALT) pathway activation. Elongation varied among iPSC clones derived from the same patient and among clones from siblings harboring identical mutations. Clonal heterogeneity was linked to genetic and environmental factors, but was not influenced by residual expression of reprogramming transgenes. Hypoxia increased telomere extension in both mutant and normal iPSCs. Additionally, telomerase-mutant iPSCs showed defective hematopoietic differentiation in vitro, mirroring the clinical phenotype observed in patients and demonstrating that human telomere diseases can be modeled utilizing iPSCs. Our data support the necessity of studying multiple clones when using iPSCs to model disease.
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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.