T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage

Laleh Talebian, Zhe Li, Yalin Guo, Justin Gaudet, Maren E. Speck, Daisuke Sugiyama, Prabhjot Kaur, Warren S. Pear, Ivan Maillard, Nancy A. Speck

    研究成果: Contribution to journalArticle査読

    57 被引用数 (Scopus)

    抄録

    The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non-DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4-CD8- double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.

    本文言語英語
    ページ(範囲)11-21
    ページ数11
    ジャーナルBlood
    109
    1
    DOI
    出版ステータス出版済み - 1 1 2007

    All Science Journal Classification (ASJC) codes

    • 生化学
    • 免疫学
    • 血液学
    • 細胞生物学

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