• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    A20 deficiency in multipotent progenitors perturbs quiescence of hematopoietic stem cells

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Publisher version
    View Source
    Access full-text PDFOpen Access
    View Source
    Check access options
    Check access options
    Author
    Nakagawa, M.M.
    Davis, H.
    Rathinam, C.V.
    Date
    2018
    Journal
    Stem Cell Research
    Publisher
    Elsevier B.V.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1016/j.scr.2018.10.020
    Abstract
    Inflammatory signals have been shown to play a critical role in controlling the maintenance and functions of hematopoietic stem cells (HSCs). While the significance of inflammation in hematopoiesis has begun to unfold, molecular mechanisms and players that govern this mode of HSC regulation remain largely unknown. The E3 ubiquitin ligase A20 has been considered as a central gatekeeper of inflammation. Here, we have specifically depleted A20 in multi-potent progenitors (MPPs) and studied its impact on hematopoiesis. Our data suggest that lack of A20 in Flt3 + progenitors causes modest alterations in hematopoietic differentiation. Analysis of hematopoietic stem and progenitor cell (HSPC) pool revealed alterations in HSPC subsets including, HSCs, MPP1, MPP2, MPP3 and MPP4. Interestingly, A20 deficiency in MPPs caused loss of HSC quiescence and compromised long-term hematopoietic reconstitution. Mechanistic studies identified that A20 deficiency caused elevated levels of Interferon-? signaling and downregulation of p57 in HSCs. In essence, these studies identified A20 as a key regulator of HSC quiescence and cell fate decisions. © 2018
    Sponsors
    We thank Drs. Bleul and Boehm for providing the Flt3-Cre mice. This work was supported by grants from the NHLBI HL132194 (CVR).
    Keyword
    Hematopoietic Stem Cells
    Ubiquitin-Protein Ligases--deficiency
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056601601&doi=10.1016%2fj.scr.2018.10.020&partnerID=40&md5=95811b47849374e41ed4c272bb0c4248; http://hdl.handle.net/10713/8829
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.scr.2018.10.020
    Scopus Count
    Collections
    UMB Open Access Articles

    entitlement

    Related articles

    • A20 deficiency in hematopoietic stem cells causes lymphopenia and myeloproliferation due to elevated Interferon-γ signals.
    • Authors: Nakagawa MM, Rathinam CV
    • Issue date: 2019 Sep 2
    • Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence.
    • Authors: Nakagawa MM, Thummar K, Mandelbaum J, Pasqualucci L, Rathinam CV
    • Issue date: 2015 Feb 9
    • Transgenic expression of BRCA1 disturbs hematopoietic stem and progenitor cells quiescence and function.
    • Authors: Bai L, Shi G, Zhang X, Dong W, Zhang L
    • Issue date: 2013 Oct 15
    • Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor.
    • Authors: Zayas J, Spassov DS, Nachtman RG, Jurecic R
    • Issue date: 2008 Apr
    • Repression of p53-target gene Bbc3/PUMA by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance.
    • Authors: Belle JI, Petrov JC, Langlais D, Robert F, Cencic R, Shen S, Pelletier J, Gros P, Nijnik A
    • Issue date: 2016 May
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    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.