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Publication : The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages.

First Author  Scott CL Year  2018
Journal  Immunity Volume  49
Issue  2 Pages  312-325.e5
PubMed ID  30076102 Mgi Jnum  J:274437
Mgi Id  MGI:6297142 Doi  10.1016/j.immuni.2018.07.004
Citation  Scott CL, et al. (2018) The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages. Immunity 49(2):312-325.e5
abstractText  Heterogeneity between different macrophage populations has become a defining feature of this lineage. However, the conserved factors defining macrophages remain largely unknown. The transcription factor ZEB2 is best described for its role in epithelial to mesenchymal transition; however, its role within the immune system is only now being elucidated. We show here that Zeb2 expression is a conserved feature of macrophages. Using Clec4f-cre, Itgax-cre, and Fcgr1-cre mice to target five different macrophage populations, we found that loss of ZEB2 resulted in macrophage disappearance from the tissues, coupled with their subsequent replenishment from bone-marrow precursors in open niches. Mechanistically, we found that ZEB2 functioned to maintain the tissue-specific identities of macrophages. In Kupffer cells, ZEB2 achieved this by regulating expression of the transcription factor LXRalpha, removal of which recapitulated the loss of Kupffer cell identity and disappearance. Thus, ZEB2 expression is required in macrophages to preserve their tissue-specific identities.
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