Transcription factor C/EBPα is required for the development of Ly6Chi monocytes but not Ly6Clo monocytes
Monocytes comprise two major subsets, Ly6Chi classical monocytes and Ly6Clo nonclassical monocytes. Notch2 signaling in Ly6Chi monocytes triggers transition to Ly6Clo monocytes, which require Nr4a1, Bcl6, Irf2, and Cebpb. By comparison, less is known about transcriptional requirements for Ly6Chi monocytes. We find transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) is highly expressed in Ly6Chi monocytes, but down-regulated in Ly6Clo monocytes. A few previous studies described the requirement of C/EBPα in the development of neutrophils and eosinophils. However, the role of C/EBPα for in vivo monocyte development has not been understood. We deleted the Cebpa +37 kb enhancer in mice, eliminating hematopoietic expression of C/EBPα, reproducing the expected neutrophil defect. Surprisingly, we also found a severe and selective loss of Ly6Chi monocytes, while preserving Ly6Clo monocytes. We find that BM progenitors from Cebpa +37-/- mice rapidly progress through the monocyte progenitor stage to develop directly into Ly6Clo monocytes even in the absence of Notch2 signaling. These results identify a previously unrecognized role for C/EBPα in maintaining Ly6Chi monocyte identity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 15 vom: 09. Apr., Seite e2315659121 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Sunkyung [VerfasserIn] |
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| Links: |
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| Themen: |
C/EBPα |
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| Anmerkungen: |
Date Completed 04.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2315659121 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37054076X |
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| 245 | 1 | 0 | |a Transcription factor C/EBPα is required for the development of Ly6Chi monocytes but not Ly6Clo monocytes |
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| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Monocytes comprise two major subsets, Ly6Chi classical monocytes and Ly6Clo nonclassical monocytes. Notch2 signaling in Ly6Chi monocytes triggers transition to Ly6Clo monocytes, which require Nr4a1, Bcl6, Irf2, and Cebpb. By comparison, less is known about transcriptional requirements for Ly6Chi monocytes. We find transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) is highly expressed in Ly6Chi monocytes, but down-regulated in Ly6Clo monocytes. A few previous studies described the requirement of C/EBPα in the development of neutrophils and eosinophils. However, the role of C/EBPα for in vivo monocyte development has not been understood. We deleted the Cebpa +37 kb enhancer in mice, eliminating hematopoietic expression of C/EBPα, reproducing the expected neutrophil defect. Surprisingly, we also found a severe and selective loss of Ly6Chi monocytes, while preserving Ly6Clo monocytes. We find that BM progenitors from Cebpa +37-/- mice rapidly progress through the monocyte progenitor stage to develop directly into Ly6Clo monocytes even in the absence of Notch2 signaling. These results identify a previously unrecognized role for C/EBPα in maintaining Ly6Chi monocyte identity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a C/EBPα | |
| 650 | 4 | |a classical monocyte | |
| 650 | 4 | |a neutrophil | |
| 650 | 4 | |a nonclassical monocyte | |
| 650 | 4 | |a transcription factor | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a CEBPA protein, mouse |2 NLM | |
| 700 | 1 | |a Chen, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Ou, Feiya |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Tian-Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Jo, Suin |e verfasserin |4 aut | |
| 700 | 1 | |a Gillanders, William E |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Theresa L |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Kenneth M |e verfasserin |4 aut | |
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