• Login
    View Item 
    •   Home
    • UA Faculty Research
    • UA Faculty Publications
    • View Item
    •   Home
    • UA Faculty Research
    • UA Faculty Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    JCI88936.pdf
    Size:
    1.871Mb
    Format:
    PDF
    Description:
    FInal Published Version
    Download
    Author
    Elagib, Kamaleldin E.
    Lu, Chih-Huan
    Mosoyan, Goar
    Khalil, Shadi
    Zasadzinska, Ewelina
    Foltz, Daniel R.
    Balogh, Peter
    Gru, Alejandro A.
    Fuchs, Deborah A.
    Rimsza, Lisa M.
    Verhoeyen, Els
    Sanso, Miriam
    Fisher, Robert P.
    Iancu-Rubin, Camelia
    Goldfarb, Adam N.
    Show allShow less
    Affiliation
    Univ Arizona, Coll Med, Dept Pathol
    Issue Date
    2017-05-08
    
    Metadata
    Show full item record
    Publisher
    AMER SOC CLINICAL INVESTIGATION INC
    Citation
    Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition 2017, 127 (6):2365 Journal of Clinical Investigation
    Journal
    Journal of Clinical Investigation
    Rights
    Copyright © 2017, American Society for Clinical Investigation
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    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.
    ISSN
    0021-9738
    1558-8238
    PubMed ID
    28481226
    DOI
    10.1172/JCI88936
    Version
    Final published version
    Sponsors
    NIH [DK090926, HL130550, T32 CA009109-39]
    Additional Links
    https://www.jci.org/articles/view/88936
    ae974a485f413a2113503eed53cd6c53
    10.1172/JCI88936
    Scopus Count
    Collections
    UA Faculty Publications

    entitlement

    Related articles

    • Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation.
    • Authors: Elagib KE, Rubinstein JD, Delehanty LL, Ngoh VS, Greer PA, Li S, Lee JK, Li Z, Orkin SH, Mihaylov IS, Goldfarb AN
    • Issue date: 2013 Dec 23
    • PDCD2 knockdown inhibits erythroid but not megakaryocytic lineage differentiation of human hematopoietic stem/progenitor cells.
    • Authors: Kokorina NA, Granier CJ, Zakharkin SO, Davis S, Rabson AB, Sabaawy HE
    • Issue date: 2012 Dec
    • Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes.
    • Authors: Lecine P, Villeval JL, Vyas P, Swencki B, Xu Y, Shivdasani RA
    • Issue date: 1998 Sep 1
    • Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates.
    • Authors: Murray NA, Roberts IA
    • Issue date: 1996 Jul
    • miR-125b modulates megakaryocyte maturation by targeting the cell-cycle inhibitor p19<sup>INK4D</sup>.
    • Authors: Qu M, Fang F, Zou X, Zeng Q, Fan Z, Chen L, Yue W, Xie X, Pei X
    • Issue date: 2016 Oct 20
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.