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C/EBPβ is required for 'emergency' granulopoiesis
Abstract
During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors. 'Steady-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Here we show that large numbers of granulocytes were generated from C/EBPalpha-deficient progenitors after cytokine stimulation in vivo. Cytokine treatment or fungal infection induced upregulation of C/EBPbeta but not C/EBPalpha or C/EBPepsilon transcripts in granulocyte progenitors, and C/EBPbeta-deficient progenitors showed decreased emergency-induced granulopoiesis in vitro and in vivo. C/EBPbeta inhibited proliferation less severely than did C/EBPalpha. These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.
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“granulocyte cell-stimulating factor–mediated activation of STAT3 induces granulocytic progenitor proliferation through transcriptional upregulation of CCAAT/enhancer-binding protein (C/EBP)β and c-Myc”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hirai et al., 2006
In the citing paper
“The mechanisms regulating “emergency” myelopoiesis are likely multifactorial, and transcriptional regulators such as C/EBPβ have also been implicated as drivers of hematopoietic responses to injury and infection (Hirai et al., 2006; Hirai et al., 2015).”
From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Hirai et al., 2006
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Kabir, A. U., Subramanian, M., Wu, J., Kim, M., Krchma, K., Wang, X., Halabi, C. M., Pan, H., Wickline, S. A., Fremont, D. H., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.02.530835
MRC2 expression modulates metabolism in acute myeloid leukemia stem cells
Mills, T., Arnone, M., Görsch, E., Poeschel, S., Winter, S., Kübler, J. V., Kimmich, L. M., Büttner, F., Weller, J. F., Rudat, S., et al. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.218068 · Cited by 2
Metadata
- Authors
- Hirai, H., Zhang, P., Dayaram, T., Hetherington, C. J., Mizuno, S.-I., Imanishi, J., Akashi, K., & Tenen, D. G.
- Affiliations
- Harvard University (US)
- Kyushu University (JP)
- Corresponding author
- Tenen, Daniel G
- Venue
- Nature Immunology
- Published
- 2006-06-04
- Volume
- 7
- Issue
- 7
- Pages
- 732-739
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1986957385
- Cited by
- 425
- References
- 61
- Citations by year
- 2026: 23 · 2025: 22 · 2024: 29 · 2023: 24 · 2022: 15 · 2021: 22 · 2020: 32 · 2019: 19 · 2018: 21 · 2017: 21 · 2016: 24 · 2015: 25 · 2014: 22 · 2013: 23 · 2012: 20
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL056745, HL56745)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- C/EBPβ, emergency granulopoiesis, C/EBPα, granulocyte progenitors, transcription factors, cytokine induction, fungal infection, granulocytic differentiation, progenitor cell proliferation
- MeSH terms
- Animals, Candidiasis, Cell Cycle, Cell Differentiation, Cells, Cultured, Colony-Forming Units Assay, Estradiol, Granulocytes, Hematopoiesis, Hematopoietic Stem Cells, Humans, Infections, Interleukin-3, Mice, Inbred C57BL, Radiation Chimera, Receptors, Estrogen, Recombinant Fusion Proteins, Transduction, Genetic, Up-Regulation, Granulocyte-Macrophage Colony-Stimulating Factor, Granulocyte Colony-Stimulating Factor, K562 Cells, Animals, Congenic, CCAAT-Enhancer-Binding Proteins, CCAAT-Enhancer-Binding Protein-alpha, CCAAT-Enhancer-Binding Protein-beta, Mice
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