GSE122393
The epigenetic regulator Histone Deacetylase 3 regulates the ontogeny and maintenance of tissue-resident macrophage [RNA-Seq]
Tissue-resident macrophages (TRMs) play central roles in local tissue development and immunity. However, how to control TRM ontogeny and maintenance remains unclear. We performed transcriptional and histone modification analyses of alveolar macrophages in mice with myeloid-specific (Csf1rCre) deletion of HDAC3 using bulk RNA-seq, single-cell RNA-seq and ChIP-seq. We report that HDAC3 deficiency results in metabolic disorders and increased cell death of the fetal lung TRMs, which is partially regulated through directly targeting PPAR-?. Although the loss of AMs in the absence of HDAC3 is not AM subset specific, the transcriptome changes in HDAC3 deficient AM subsets are different. We propose that HDAC3 serves a key epigenetic regulator that controls embryonic TRM ontogeny and maintenance. Overall design: RNA-sequencing of Csf1rCre+HDAC3fl/fl and Csf1rCre-HDAC3fl/fl fetal preAMs at E18.5