| First Author | Czubala MA | Year | 2024 |
| Journal | J Biol Chem | Volume | 300 |
| Issue | 5 | Pages | 107244 |
| PubMed ID | 38556087 | Mgi Jnum | J:357267 |
| Mgi Id | MGI:7639014 | Doi | 10.1016/j.jbc.2024.107244 |
| Citation | Czubala MA, et al. (2024) Tissue-specific transcriptional programming of macrophages controls the microRNA transcriptome targeting multiple functional pathways. J Biol Chem 300(5):107244 |
| abstractText | Recent interest in the biology and function of peritoneal tissue resident macrophages (pMPhi) has led to a better understanding of their cellular origin, programming, and renewal. The programming of pMPhi is dependent on microenvironmental cues and tissue-specific transcription factors, including GATA6. However, the contribution of microRNAs remains poorly defined. We conducted a detailed analysis of the impact of GATA6 deficiency on microRNA expression in mouse pMPhi. Our data suggest that for many of the pMPhi, microRNA composition may be established during tissue specialization and that the effect of GATA6 knockout is largely unable to be rescued in the adult by exogenous GATA6. The data are consistent with GATA6 modulating the expression pattern of specific microRNAs, directly or indirectly, and including miR-146a, miR-223, and miR-203 established by the lineage-determining transcription factor PU.1, to achieve a differentiated pMPhi phenotype. Lastly, we showed a significant dysregulation of miR-708 in pMPhi in the absence of GATA6 during homeostasis and in response to LPS/IFN-gamma stimulation. Overexpression of miR-708 in mouse pMPhi in vivo altered 167 mRNA species demonstrating functional downregulation of predicted targets, including cell immune responses and cell cycle regulation. In conclusion, we demonstrate dependence of the microRNA transcriptome on tissue-specific programming of tissue macrophages as exemplified by the role of GATA6 in pMPhi specialization. |
