ArticleBlood2011
Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 106 citations in OpenAlex.
- Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation.Blood advances · 2020Trial
- Sea-blue histiocytosis and thrombocytopenia successfully treated with an mTORC1 inhibitor: a case report.Annals of hematology · 2026Article
- The Kifc3 Motor Protein Controls Centrosomal Factor Cep192 in Ontogenic Coordination of Megakaryocyte Development.bioRxiv : the preprint server for biology · 2026Article
- `Inflammatory mediators differentially regulate megakaryopoiesis and thrombopoiesis in myelofibrosis and essential thrombocythemia.Scientific reports · 2025Article
- Emerging Roles of Megakaryocytes in Immune Regulation and Potential Therapeutic Prospects.Cells · 2025Review
- Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis.Stem cell reports · 2025Article
- Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- Reduced platelet glycoprotein Ibα shedding accelerates thrombopoiesis and COX-1 recovery: implications for aspirin dosing regimen.Haematologica · 2023Article
- Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes.The Journal of clinical investigation · 2022Article
- Human platelets display dysregulated sepsis-associated autophagy, induced by altered LC3 protein-protein interaction of the Vici-protein EPG5.Autophagy · 2022Article
- Fetal vs adult megakaryopoiesis.Blood · 2022Article
- Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitro.Blood advances · 2022Article
- Occurrence and role of lung megakaryocytes in infection and inflammation.Frontiers in immunology · 2022Review
- Megakaryoblastic leukemia: a study on novel role of clinically significant long non-coding RNA signatures in megakaryocyte development during treatment with phorbol ester.Cancer immunology, immunotherapy : CII · 2021Article
- Involvement of autophagy in diosgenin‑induced megakaryocyte differentiation in human erythroleukemia cells.Molecular medicine reports · 2021Article
- Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and plateletsHaematologica · 2021Review
- Development of platelet replacement therapy using human induced pluripotent stem cells.Development, growth & differentiation · 2021Review
- Observational Study on Variation of Longitudinal Platelet Counts in Calves over the First 14 Days of Life and Reference Intervals from Cross-Sectional Platelet and Leukocyte Counts in Dairy Calves up to Two Months of Age.Animals : an open access journal from MDPI · 2021Article
- TMEA, a Polyphenol inFrontiers in cell and developmental biology · 2021Article
- Dengue Virus Dysregulates Master Transcription Factors and PI3K/AKT/mTOR Signaling Pathway in Megakaryocytes.Frontiers in cellular and infection microbiology · 2021Article
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8 authors at 4 institutions in 1 country.
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Abstract
Multiple observations support the existence of developmental differences in megakaryocytopoiesis. We have previously shown that neonatal megakaryocyte (MK) progenitors are hyperproliferative and give rise to MKs smaller and of lower ploidy than adult MKs. Based on these characteristics, neonatal MKs have been considered immature. The molecular mechanisms underlying these differences are unclear, but contribute to the pathogenesis of disorders of neonatal megakaryocytopoiesis. In the present study, we demonstrate that low-ploidy neonatal MKs, contrary to traditional belief, are more mature than adult low-ploidy MKs. These mature MKs are generated at a 10-fold higher rate than adult MKs, and result from a developmental uncoupling of proliferation, polyploidization, and terminal differentiation. This pattern is associated with up-regulated thrombopoietin (TPO) signaling through mammalian target of rapamycin (mTOR) and elevated levels of full-length GATA-1 and its targets. Blocking of mTOR with rapamycin suppressed the maturation of neonatal MKs without affecting ploidy, in contrast to the synchronous inhibition of polyploidization and cytoplasmic maturation in adult MKs. We propose that these mechanisms allow fetuses/neonates to populate their rapidly expanding bone marrow and intravascular spaces while maintaining normal platelet counts, but also set the stage for disorders restricted to fetal/neonatal MK progenitors, including the Down syndrome-transient myeloproliferative disorder and the thrombocytopenia absent radius syndrome.
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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.