The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and survival of Ly6C− monocytes

By R. Hanna, Leo M. Carlin, Harper G. Hubbeling, Dominika Nąckiewicz, A. Green, J. Punt, F. Geissmann, C. Hedrick. Nature Immunology, 2011

627 citations recorded by the source corpus.

The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C− monocytes. Ly6C− monocytes, which function in a surveillance role in circulation, were absent from Nr4a1−/− mice. Normal numbers of myeloid progenitor cells were present in Nr4a1−/− mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from Nr4a1−/− mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C− monocytes remaining in the bone marrow of Nr4a1−/− mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C− monocytes.

Subfields: Cellular and Molecular Neuroscience, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ee04ee3723c037b1801dd3840eb4dd76ec89e20b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. I. Tabas

In Immunology

1. M. Guilliams
2. A. Mildner
3. P. Italiani
4. D. Boraschi
5. Steffen Jung
6. A. Lichtman
7. F. Geissmann
8. C. Varol

In Molecular Biology

1. A. Lichtman
2. I. Tabas
3. Bart Staels
4. A. Mildner
5. Steffen Jung
6. C. Varol
7. P. Italiani
8. F. Geissmann

Citations in the corpus

• Monocyte-Macrophages and T Cells in Atherosclerosis (2017, positive): “The realization that physiologic mechanisms underlying the resolution of inflammation are impaired in the human plaque environment and that pro-resolution therapy might not compromise host defense as much as anti-inflammatory therapy has led to active work in developing therapies based on the delive”
• Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal (2013, methodology): “Earlier observations that Ly6Clow monocytes crawl on endothelia (Auffray et al., 2007; Hanna et al., 2011; Li et al., 2012; Sumagin et al., 2010) and do not contribute to the pool of inflammatory monocytes that extravasate to give inflammatory macrophages and DCs in response to listeria infection…”
• From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “bone marrow but not in blood or spleen (52), but does not alter the number of macrophages within tissues (53).”
• Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis (2012, positive): “Interestingly, CSF-1 has been reported to induce the NOR1 (Pei et al., 2005), an orphan nuclear receptor and member of the steroid thyroid receptor family, which also comprises Nur77 (Nr4A) that was recently implicated in the control of Ly6C − monocyte survival (Hanna et al., 2011).”
• Origin and Functions of Tissue Macrophages (2014, background): “…Ly6chi monocytes, which appear to be directly descendent from Ly6c+ monocyte progenitors, and (2) Ly6clo nonclassical monocytes, which differentiate from Ly6chi monocytes through an Nr4a1-dependent transcriptional program (Hanna et al., 2011; Hettinger et al., 2013; Yona et al., 2013) (Figure 2).”
• iPSC-derived human microglia-like cells to study neurological diseases (2017, neutral): “When compared to monocytes, iMGLs express the myeloid genes, RUNX1, PU.1, and CSF1R (Figure S3C), but do not express monocyte-specific transcription factors, IRF1, KLF4, NR4A1 (Lavin et al., 2014, Abdollahi et al., 1991, Hanna et al., 2011) (Figure S3D).”
• Macrophage phenotypes in atherosclerosis (2014, background): “Among them, Nur77 (NR4A1) is highly expressed in mouse Ly6C monocytes and macrophages (111) and suggested to be required for monocyte differentiation into alternative M2 macrophages (112, 113).”
• Macrophages: development and tissue specialization. (2015, background): “The generation of Ly6Clow cells requires the transcription factor NR4a1 (Nur77) (67).”
• Developmental and Functional Heterogeneity of Monocytes. (2018, background): “Subsequently, both genes were shown to be involved in Ly6C monocyte generation (Hanna et al., 2011; Mildner et al., 2017; Tamura et al., 2017; Thomas et al., 2016).”
• Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19 (2020, neutral): “, 2015), unless these cells strongly adhere to the endothelium or conversion of classical into non-classical monocytes is stuck (Hanna et al., 2011; Hofer et al., 2015; Selimoglu-Buet et al., 2018).”