Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Oct;100(4):665-677.
doi: 10.1189/jlb.1HI0915-398RR. Epub 2016 Apr 15.

The mirn23a microRNA cluster antagonizes B cell development

Jeffrey L Kurkewich  1 , Emmanuel Bikorimana  2 , Tan Nguyen  2 , Nathan Klopfenstein  2 , Helen Zhang  1 , William M Hallas  2 , Gwen Stayback  3 , Mary Ann McDowell  3 , Richard Dahl  4
Affiliations

The mirn23a microRNA cluster antagonizes B cell development

Jeffrey L Kurkewich et al. J Leukoc Biol. 2016 Oct.

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 the mirn23a 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.

Keywords: Trib3; hematopoiesis; lymphopoiesis; myelopoiesis.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources