cMaf supports Zeb2 expression for primitive hematopoiesis (TRM RNA-seq)

Tissue-resident macrophages (TRMs) are essential for tissue homeostasis and play a key role in disease and pathology. They originate from distinct waves of hematopoietic progenitors, including primitive, transient-definitive, and definitive hematopoiesis. We found that loss of the Zeb2 ‒165kb enhancer impairs monocyte development and alters TRM transcriptional landscapes, with only HSC-derived monocytes requiring Zeb2 for their development. In Zeb2∆‒165kb mice, primitive TRMs persist in tissues due to the lack of replacement by later hematopoietic waves, and Maf is required for maintaining Zeb2 expression in primitive macrophages.