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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1404805

NR2F6 regulates stem cell hematopoiesis and myelopoiesis in mice

Provisionally accepted
Johannes Woelk Johannes Woelk 1Hamsa Narasimhan Hamsa Narasimhan 2,3Barbara Ursula Schraml Barbara Ursula Schraml 2,3Natascha Hermann-Kleiter Natascha Hermann-Kleiter 1*
  • 1 Institute of Cell Genetics, Department for Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria, Austria
  • 2 Institute of Cardiovascular Physiology and Pathophysiology, BioMedical Center, Ludwig Maximilian University of Munich, Planegg-Martinsried, Germany
  • 3 Walter Brendel Center of Experimental Medicine, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Bavaria, Germany

The final, formatted version of the article will be published soon.

    Nuclear receptors regulate hematopoietic stem cells (HSCs) and peripheral immune cells in mice and humans. The nuclear orphan receptor NR2F6 (EAR-2) has been shown to control murine hematopoiesis. Still, detailed analysis of the distinct stem cell, myeloid, and lymphoid progenitors in the bone marrow in a genetic loss of function model remains pending. In this study, we found that adult germline Nr2f6-deficient mice contained increased percentages of total long-term and short-term HSCs, as well as a subpopulation within the lineage-biased multipotent progenitor (MPP3) cells. The loss of NR2F6 thus led to an increase in the percentage of LSK + cells. Following the differentiation from the common myeloid progenitors (CMP), the granulocyte-monocyte progenitors (GMP) were decreased, while monocyte-dendritic progenitors (MDP) were increased in Nr2f6-deficient bone marrow. Within the pre-conventional dendritic progenitors (pre-cDCs), the subpopulation of pre-cDC2s was reduced in the bone marrow of Nr2f6-deficient mice. We did not observe differences in the development of common lymphoid progenitor populations. Our findings contrast previous studies but underscore the role of NR2F6 in regulating gene expression levels during mouse bone marrow hematopoiesis and myelopoiesis.

    Keywords: Nuclear receptor NR2F6, Bone Marrow, Hematopoiesis, HSC, GMP, MDP, pre-cDC2, myleoid compartment Metrics

    Received: 21 Mar 2024; Accepted: 11 Dec 2024.

    Copyright: © 2024 Woelk, Narasimhan, Schraml and Hermann-Kleiter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Natascha Hermann-Kleiter, Institute of Cell Genetics, Department for Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria, Austria

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