ArticleThe Journal of clinical investigation2013
Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling.
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 29 papers.
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Who cites it
29 citing papers in PubMed, 64 citations in OpenAlex.
- Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management.Journal of clinical medicine · 2023Review
- Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation.Scientific reports · 2022Article
- Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.Frontiers in oncology · 2022Article
- Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias.Journal of clinical medicine · 2021Review
- The Opportunities and Challenges regarding Induced Platelets from Human Pluripotent Stem Cells.Stem cells international · 2021Review
- Diagnosis of Inherited Platelet Disorders on a Blood Smear.Journal of clinical medicine · 2020Article
- Modeling blood diseases with human induced pluripotent stem cells.Disease models & mechanisms · 2019Review
- Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury.Blood advances · 2019Article
- Human induced pluripotent stem cell models for the study and treatment of Duchenne and Becker muscular dystrophies.Therapeutic advances in neurological disorders · 2019Review
- Transcription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision.Stem cell reports · 2018Article
- Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis accelerating recovery from thrombocytopenia.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim.EMBO molecular medicine · 2018Article
- Hereditary thrombocytopenias: a growing list of disorders.Hematology. American Society of Hematology. Education Program · 2017Review
- Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte-specific reporter line in zebrafish.Leukemia · 2017Article
- Selective Inhibition of ADAM17 Efficiently Mediates Glycoprotein Ibα Retention During Ex Vivo Generation of Human Induced Pluripotent Stem Cell-Derived Platelets.Stem cells translational medicine · 2017Article
- Concise Review: Getting to the Core of Inherited Bone Marrow Failures.Stem cells (Dayton, Ohio) · 2017Review
- Induced Pluripotent Stem Cells: Global Research Trends.BioResearch open access · 2017Review
- Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency.Stem cell reports · 2016Article
- hiPSC-derived iMSCs: NextGen MSCs as an advanced therapeutically active cell resource for regenerative medicine.Journal of cellular and molecular medicine · 2016Review
- Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor-mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl(-/-) mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT.
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