• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    RUNX1B expression is highly heterogeneous and distinguishes megakaryocytic and erythroid lineage fate in adult mouse hematopoiesis

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Draper, Julia E
    Sroczynska, Patrycja
    Tsoulaki, Olga
    Leong, Hui Sun
    Fadlullah, Muhammad Z H
    Miller, Crispin J
    Kouskoff, Valerie
    Lacaud, Georges
    Affiliation
    Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom
    Issue Date
    2016-01
    
    Metadata
    Show full item record
    Abstract
    The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct protein isoforms. The activities and specific relevance of these two promoters in adult hematopoiesis remain to be fully elucidated. Utilizing a dual reporter mouse model we demonstrate that the distal P1 promoter is broadly active in adult hematopoietic stem and progenitor cell (HSPC) populations. By contrast the activity of the proximal P2 promoter is more restricted and its upregulation, in both the immature Lineage- Sca1high cKithigh (LSK) and bipotential Pre-Megakaryocytic/Erythroid Progenitor (PreMegE) populations, coincides with a loss of erythroid (Ery) specification. Accordingly the PreMegE population can be prospectively separated into "pro-erythroid" and "pro-megakaryocyte" populations based on Runx1 P2 activity. Comparative gene expression analyses between Runx1 P2+ and P2- populations indicated that levels of CD34 expression could substitute for P2 activity to distinguish these two cell populations in wild type (WT) bone marrow (BM). Prospective isolation of these two populations will enable the further investigation of molecular mechanisms involved in megakaryocytic/erythroid (Mk/Ery) cell fate decisions. Having characterized the extensive activity of P1, we utilized a P1-GFP homozygous mouse model to analyze the impact of the complete absence of Runx1 P1 expression in adult mice and observed strong defects in the T cell lineage. Finally, we investigated how the leukemic fusion protein AML1-ETO9a might influence Runx1 promoter usage. Short-term AML1-ETO9a induction in BM resulted in preferential P2 upregulation, suggesting its expression may be important to establish a pre-leukemic environment.
    Citation
    RUNX1B expression is highly heterogeneous and distinguishes megakaryocytic and erythroid lineage fate in adult mouse hematopoiesis. 2016, 12 (1):e1005814 PLoS Genet
    Journal
    PLoS Genetics
    URI
    http://hdl.handle.net/10541/600533
    DOI
    10.1371/journal.pgen.1005814
    PubMed ID
    26808730
    Type
    Article
    Language
    en
    ISSN
    1553-7404
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pgen.1005814
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Mouse RUNX1C regulates premegakaryocytic/erythroid output and maintains survival of megakaryocyte progenitors.
    • Authors: Draper JE, Sroczynska P, Leong HS, Fadlullah MZH, Miller C, Kouskoff V, Lacaud G
    • Issue date: 2017 Jul 20
    • A novel prospective isolation of murine fetal liver progenitors to study in utero hematopoietic defects.
    • Authors: Draper JE, Sroczynska P, Fadlullah MZH, Patel R, Newton G, Breitwieser W, Kouskoff V, Lacaud G
    • Issue date: 2018 Jan
    • Nonredundant roles for Runx1 alternative promoters reflect their activity at discrete stages of developmental hematopoiesis.
    • Authors: Bee T, Swiers G, Muroi S, Pozner A, Nottingham W, Santos AC, Li PS, Taniuchi I, de Bruijn MF
    • Issue date: 2010 Apr 15
    • Developmentally regulated promoter-switch transcriptionally controls Runx1 function during embryonic hematopoiesis.
    • Authors: Pozner A, Lotem J, Xiao C, Goldenberg D, Brenner O, Negreanu V, Levanon D, Groner Y
    • Issue date: 2007 Jul 12
    • The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.
    • Authors: Sroczynska P, Lancrin C, Kouskoff V, Lacaud G
    • Issue date: 2009 Dec 17
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    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.