Mus musculus strain:C57BL/6J Raw sequence reads. Mus musculus strain:C57BL/6J

Tissue-resident macrophages require specific milieus for their homeostasis, yet these essential niches are largely undescribed. Peritoneal cavity-resident macrophages depend on GATA6, a master transcription factor induced by the vitamin A metabolite, retinoic acid. We discovered that the GATA6 transcriptional program is a universal feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6+ macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms Tumor 1 (WT1). Wt1+ stromal cells proved critical for cavity macrophage homeostasis and GATA6 maintenance in vivo. Thus, the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages is supported by Wt1+ mesothelial and fibroblastic stromal cells.