The mirn23a microRNA cluster antagonizes B cell development

Jeffrey L. Kurkewich, Emmanuel Bikorimana, Tan Nguyen, Nathan Klopfenstein, Helen Zhang, William M. Hallas, Gwen Stayback, Mary Ann McDowell, Richard Dahl

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Ablation of microRNA synthesis by deletion of the microRNA-processing enzyme Dicer has demonstrated that microRNAs are necessary for normal hematopoietic differentiation and function. However, it is still unclear which specific microRNAs are required for hematopoiesis and at what developmental stages they are necessary. This is especially true for immune cell development. We previously observed that overexpression of the products of themirn23a gene (microRNA-23a, -24-2, and 27a) in hematopoietic progenitors increased myelopoiesis with a reciprocal decrease in B lymphopoiesis, both in vivo and in vitro. In this study, we generated a microRNA-23a, -24-2, and 27a germline knockout mouse to determine whether microRNA-23a, -24-2, and 27a expression was essential for immune cell development. Characterization of hematopoiesis in microRNA-23a, -24-2, and 27a-/- mice revealed a significant increase in B lymphocytes in both the bone marrow and the spleen, with a concomitant decrease in myeloid cells (monocytes/ granulocytes). Analysis of the bone marrow progenitor populations revealed a significant increase in common lymphoid progenitors and a significant decrease in both bone marrow common myeloid progenitors and granulocyte monocyte progenitors. Gene-expression analysis of primary hematopoietic progenitors and multipotent erythroid myeloid lymphoid cells showed that microRNA-23a, -24-2, and 27a regulates essential B cell gene-expression networks. Overexpression of microRNA-24-2 target Tribbles homolog 3 can recapitulate the microRNA-23a, -24-2, and 27a-/- phenotype in vitro, suggesting that increased B cell development in microRNA-23a, -24-2, and 27a null mice can be partially explained by a Tribbles homolog 3-dependent mechanism. Data from microRNA-23a, -24-2, and 27a-/- mice support a critical role for this microRNA cluster in regulating immune cell populations through repression of B lymphopoiesis.

Original languageEnglish (US)
Pages (from-to)665-677
Number of pages13
JournalJournal of Leukocyte Biology
Volume100
Issue number4
DOIs
StatePublished - Oct 2016

Keywords

  • Hematopoiesis
  • Lymphopoiesis
  • Myelopoiesis
  • Trib3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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  • Cite this

    Kurkewich, J. L., Bikorimana, E., Nguyen, T., Klopfenstein, N., Zhang, H., Hallas, W. M., Stayback, G., McDowell, M. A., & Dahl, R. (2016). The mirn23a microRNA cluster antagonizes B cell development. Journal of Leukocyte Biology, 100(4), 665-677. https://doi.org/10.1189/jlb.1HI0915-398RR