cMaf supports Zeb2 expression for primitive hematopoiesis (Multiome)

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. Overall design: Fetal Liver CD45.2+CD64+ cells were isolated from E12.5 wildtype and KO embryos. Single nuclei were extracted and submitted for snRNA- and scATAC-seq sequencing using 10X genomics multiomic platform.