ArticleThe Journal of clinical investigation2017
Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Targeting IGF2BP3 in Cancer: From Molecular Structure and Biology to Early Drug Discovery.International journal of molecular sciences · 2026Review
- The MLLT3 YEATS domain binds histone marks (H3K9/18/27ac/cr) and ncRNA (7SK), linking transcription and RNA signaling to regulate hematopoiesis.Cell reports · 2026Article
- The Kifc3 Motor Protein Controls Centrosomal Factor Cep192 in Ontogenic Coordination of Megakaryocyte Development.bioRxiv : the preprint server for biology · 2026Article
- Combinatorial inhibition of IGF2BP3-regulated receptor tyrosine kinases offers a new therapeutic strategy for triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- The molecular mechanism of IGF2BP3 promoting the malignant progression of lung cancer.Cancer cell international · 2026Review
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 2025Article
- Fusion oncoproteins and cooperating mutations define disease phenotypes in NUP98-rearranged leukemia.Blood · 2025Article
- The MLLT3 YEATS domain is a dual reader of histone marks (H3K9/18/27ac/cr) and ncRNA (7SK), linking epigenetic and RNA signaling to regulate hematopoiesis.bioRxiv : the preprint server for biology · 2025Article
- IGF2BP3 Modulates mRNA Splicing and Stability to Promote Trophoblast Progression via Interaction with PDE3A and Suppression by miR-196a-5p in Preeclampsia.Biomedicines · 2025Article
- IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma.JID innovations : skin science from molecules to population health · 2025Article
- Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma.Nature communications · 2024Article
- Article
- Aberrant stem cell and developmental programs in pediatric leukemia.Frontiers in cell and developmental biology · 2024Review
- Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation.Nature cardiovascular research · 2023Article
- Targeting IGF2BP3 in Cancer.International journal of molecular sciences · 2023Review
- Age-restricted functional and developmental differences of neonatal platelets.Journal of thrombosis and haemostasis : JTH · 2022Article
- Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes.The Journal of clinical investigation · 2022Article
- Fetal vs adult megakaryopoiesis.Blood · 2022Article
- Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Hematopoietic transitions that accompany fetal development, such as erythroid globin chain switching, play important roles in normal physiology and disease development. In the megakaryocyte lineage, human fetal progenitors do not execute the adult morphogenesis program of enlargement, polyploidization, and proplatelet formation. Although these defects decline with gestational stage, they remain sufficiently severe at birth to predispose newborns to thrombocytopenia. These defects may also contribute to inferior platelet recovery after cord blood stem cell transplantation and may underlie inefficient platelet production by megakaryocytes derived from pluripotent stem cells. In this study, comparison of neonatal versus adult human progenitors has identified a blockade in the specialized positive transcription elongation factor b (P-TEFb) activation mechanism that is known to drive adult megakaryocyte morphogenesis. This blockade resulted from neonatal-specific expression of an oncofetal RNA-binding protein, IGF2BP3, which prevented the destabilization of the nuclear RNA 7SK, a process normally associated with adult megakaryocytic P-TEFb activation. Knockdown of IGF2BP3 sufficed to confer both phenotypic and molecular features of adult-type cells on neonatal megakaryocytes. Pharmacologic inhibition of IGF2BP3 expression via bromodomain and extraterminal domain (BET) inhibition also elicited adult features in neonatal megakaryocytes. These results identify IGF2BP3 as a human ontogenic master switch that restricts megakaryocyte development by modulating a lineage-specific P-TEFb activation mechanism, revealing potential strategies toward enhancing platelet production.
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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.