ArticlePloS one2015
Dysregulation of the Transforming Growth Factor β Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Overexpression of FRA1 (Cells · 2023Article
- Inflammation fuels bone marrow exhaustion caused by Samd9l mutation.The Journal of clinical investigation · 2022Article
- Review
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- Preliminary RNA-microarray analysis of long non-coding RNA expression in abnormally invasive placenta.Experimental and therapeutic medicine · 2021Article
- Differentiation of human induced pluripotent stem cells into erythroid cells.Stem cell research & therapy · 2020Review
- Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia.Science translational medicine · 2020Article
- Inflammatory manifestations in patients with Shwachman-Diamond syndrome: A novel phenotype.American journal of medical genetics. Part A · 2020Article
- Steroid resistance in Diamond Blackfan anemia associates with p57Kip2 dysregulation in erythroid progenitors.The Journal of clinical investigation · 2020Article
- Therapeutic discovery for marrow failure with MDS predisposition using pluripotent stem cells.JCI insight · 2019Article
- Recent Updates on Induced Pluripotent Stem Cells in Hematological Disorders.Stem cells international · 2019Review
- Critical Issues in Diamond-Blackfan Anemia and Prospects for Novel Treatment.Hematology/oncology clinics of North America · 2018Review
- Emerging Therapeutic Approaches for Diamond Blackfan Anemia.Current gene therapy · 2018Review
- Li-Fraumeni Syndrome Disease Model: A Platform to Develop Precision Cancer Therapy Targeting Oncogenic p53.Trends in pharmacological sciences · 2017Review
- Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors.Science translational medicine · 2017Article
- Concise Review: Getting to the Core of Inherited Bone Marrow Failures.Stem cells (Dayton, Ohio) · 2017Review
- Article
- Modeling Cancer with Pluripotent Stem Cells.Trends in cancer · 2016Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome with clinical features of red cell aplasia and variable developmental abnormalities. Most affected patients have heterozygous loss of function mutations in ribosomal protein genes but the pathogenic mechanism is still unknown. We generated induced pluripotent stem cells from DBA patients carrying RPS19 or RPL5 mutations. Transcriptome analysis revealed the striking dysregulation of the transforming growth factor β (TGFβ) signaling pathway in DBA lines. Expression of TGFβ target genes, such as TGFBI, BAMBI, COL3A1 and SERPINE1 was significantly increased in the DBA iPSCs. We quantified intermediates in canonical and non-canonical TGFβ pathways and observed a significant increase in the levels of the non-canonical pathway mediator p-JNK in the DBA iPSCs. Moreover, when the mutant cells were corrected by ectopic expression of WT RPS19 or RPL5, levels of p-JNK returned to normal. Surprisingly, nuclear levels of SMAD4, a mediator of canonical TGFβ signaling, were decreased in DBA cells due to increased proteolytic turnover. We also observed the up-regulation of TGFβ1R, TGFβ2, CDKN1A and SERPINE1 mRNA, and the significant decrease of GATA1 mRNA in the primitive multilineage progenitors. In summary our observations identify for the first time a dysregulation of the TGFβ pathway in the pathobiology of DBA.
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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.