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

10 Citations (Scopus)

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 1 2016

Fingerprint

MicroRNAs
B-Lymphocytes
Lymphopoiesis
Bone Marrow
Hematopoiesis
Myeloid Cells
Monocytes
Lymphoid Progenitor Cells
Ribonuclease III
Myelopoiesis
Myeloid Progenitor Cells
Gene Expression
Granulocyte Precursor Cells
Erythroid Cells
Gene Regulatory Networks
Granulocytes
Knockout Mice
Population
Spleen
Lymphocytes

Keywords

  • Hematopoiesis
  • Lymphopoiesis
  • Myelopoiesis
  • Trib3

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Kurkewich, J. L., Bikorimana, E., Nguyen, T., Klopfenstein, N., Zhang, H., Hallas, W. M., ... 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

The mirn23a microRNA cluster antagonizes B cell development. / Kurkewich, Jeffrey L.; Bikorimana, Emmanuel; Nguyen, Tan; Klopfenstein, Nathan; Zhang, Helen; Hallas, William M.; Stayback, Gwen; McDowell, Mary Ann; Dahl, Richard.

In: Journal of Leukocyte Biology, Vol. 100, No. 4, 01.10.2016, p. 665-677.

Research output: Contribution to journalArticle

Kurkewich, JL, Bikorimana, E, Nguyen, T, Klopfenstein, N, Zhang, H, Hallas, WM, Stayback, G, McDowell, MA & Dahl, R 2016, 'The mirn23a microRNA cluster antagonizes B cell development', Journal of Leukocyte Biology, vol. 100, no. 4, pp. 665-677. https://doi.org/10.1189/jlb.1HI0915-398RR
Kurkewich JL, Bikorimana E, Nguyen T, Klopfenstein N, Zhang H, Hallas WM et al. The mirn23a microRNA cluster antagonizes B cell development. Journal of Leukocyte Biology. 2016 Oct 1;100(4):665-677. https://doi.org/10.1189/jlb.1HI0915-398RR
Kurkewich, Jeffrey L. ; Bikorimana, Emmanuel ; Nguyen, Tan ; Klopfenstein, Nathan ; Zhang, Helen ; Hallas, William M. ; Stayback, Gwen ; McDowell, Mary Ann ; Dahl, Richard. / The mirn23a microRNA cluster antagonizes B cell development. In: Journal of Leukocyte Biology. 2016 ; Vol. 100, No. 4. pp. 665-677.
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