| First Author | Kim S | Year | 2024 |
| Journal | Proc Natl Acad Sci U S A | Volume | 121 |
| Issue | 15 | Pages | e2315659121 |
| PubMed ID | 38564635 | Mgi Jnum | J:354615 |
| Mgi Id | MGI:7736145 | Doi | 10.1073/pnas.2315659121 |
| Citation | Kim S, et al. (2024) Transcription factor C/EBPalpha is required for the development of Ly6C(hi) monocytes but not Ly6C(lo) monocytes. Proc Natl Acad Sci U S A 121(15):e2315659121 |
| abstractText | Monocytes comprise two major subsets, Ly6C(hi) classical monocytes and Ly6C(lo) nonclassical monocytes. Notch2 signaling in Ly6C(hi) monocytes triggers transition to Ly6C(lo) monocytes, which require Nr4a1, Bcl6, Irf2, and Cebpb. By comparison, less is known about transcriptional requirements for Ly6C(hi) monocytes. We find transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) is highly expressed in Ly6C(hi) monocytes, but down-regulated in Ly6C(lo) monocytes. A few previous studies described the requirement of C/EBPalpha in the development of neutrophils and eosinophils. However, the role of C/EBPalpha for in vivo monocyte development has not been understood. We deleted the Cebpa +37 kb enhancer in mice, eliminating hematopoietic expression of C/EBPalpha, reproducing the expected neutrophil defect. Surprisingly, we also found a severe and selective loss of Ly6C(hi) monocytes, while preserving Ly6C(lo) monocytes. We find that BM progenitors from Cebpa +37(-/-) mice rapidly progress through the monocyte progenitor stage to develop directly into Ly6C(lo) monocytes even in the absence of Notch2 signaling. These results identify a previously unrecognized role for C/EBPalpha in maintaining Ly6C(hi) monocyte identity. |
