The mirn23a microRNA cluster antagonizes B cell development.
Jeffrey L Kurkewich1, Emmanuel Bikorimana2, Tan Nguyen2
1Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, Indiana, USA.
Journal of Leukocyte Biology
|April 17, 2016
Summary
The microRNA-23a, -24-2, and 27a cluster is essential for regulating immune cell development. Deleting this cluster increases B lymphocytes while decreasing myeloid cells, highlighting its role in immune cell population balance.
Area of Science:
- Molecular Biology
- Immunology
- Developmental Biology
Background:
- MicroRNAs (miRNAs) are crucial for hematopoietic differentiation and function, as shown by Dicer enzyme ablation.
- Specific miRNAs and their developmental roles in hematopoiesis, particularly for immune cell development, remain largely uncharacterized.
- Previous studies indicated that overexpressing the miR-23a, -24-2, and -27a cluster promotes myelopoiesis and inhibits B lymphopoiesis.
Purpose of the Study:
- To investigate the essential role of the microRNA-23a, -24-2, and -27a cluster in immune cell development.
- To determine the impact of deleting this miRNA cluster on hematopoietic progenitor populations and immune cell differentiation.
Main Methods:
- Generation of a germline knockout mouse model lacking the microRNA-23a, -24-2, and -27a cluster (miR-23a, -24-2, -27a-/-).
- Comprehensive characterization of hematopoiesis in knockout mice, including analysis of bone marrow and spleen cell populations.
- Gene-expression analysis of primary hematopoietic progenitors and multipotent cells; investigation of Tribbles homolog 3 (TRIB3) as a potential target.
Main Results:
- miR-23a, -24-2, -27a-/- mice exhibited a significant increase in B lymphocytes and a decrease in myeloid cells (monocytes/granulocytes).
- Analysis of progenitor populations revealed an increase in common lymphoid progenitors and a decrease in common myeloid and granulocyte-monocyte progenitors.
- Gene-expression profiling indicated that the miR-23a, -24-2, -27a cluster regulates key B cell gene-expression networks; TRIB3 overexpression mimicked the knockout phenotype.
Conclusions:
- The microRNA-23a, -24-2, and -27a cluster plays a critical role in regulating immune cell populations.
- This miRNA cluster represses B lymphopoiesis, contributing to the balance between lymphoid and myeloid cell development.
- The observed phenotype in knockout mice may be partially mediated by the microRNA-24-2 target, Tribbles homolog 3.
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