Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis Journal Article
| Authors: | Yao, Y.; Liu, Q.; Adrianto, I.; Wu, X.; Glassbrook, J.; Khalasawi, N.; Yin, C.; Yi, Q.; Dong, Z.; Geissmann, F.; Zhou, L.; Mi, Q. S. |
| Article Title: | Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis |
| Abstract: | Alveolar macrophages (AMs) derived from embryonic precursors seed the lung before birth and self-maintain locally throughout adulthood, but are regenerated by bone marrow (BM) under stress conditions. However, the regulation of AM development and maintenance remains poorly understood. Here, we show that histone deacetylase 3 (HDAC3) is a key epigenetic factor required for AM embryonic development, postnatal homeostasis, maturation, and regeneration from BM. Loss of HDAC3 in early embryonic development affects AM development starting at E14.5, while loss of HDAC3 after birth affects AM homeostasis and maturation. Single-cell RNA sequencing analyses reveal four distinct AM sub-clusters and a dysregulated cluster-specific pathway in the HDAC3-deficient AMs. Moreover, HDAC3-deficient AMs exhibit severe mitochondrial oxidative dysfunction and deteriorative cell death. Mechanistically, HDAC3 directly binds to Pparg enhancers, and HDAC3 deficiency impairs Pparg expression and its signaling pathway. Our findings identify HDAC3 as a key epigenetic regulator of lung AM development and homeostasis. © 2020, The Author(s). |
| Keywords: | signal transduction; adult; controlled study; nonhuman; flow cytometry; genetic analysis; animal cell; mouse; animal tissue; apoptosis; gene expression; gene expression profiling; animal experiment; protein; mitochondrial membrane potential; genotype; embryo development; cell differentiation; regeneration; rna; transcription regulation; messenger rna; microarray analysis; bone; down regulation; real time polymerase chain reaction; upregulation; cell regeneration; homeostasis; retinoid x receptor alpha; peroxisome proliferator activated receptor gamma; cell metabolism; oxidative phosphorylation; embryonic development; lung alveolus macrophage; enzyme deficiency; histone deacetylase 3; cell; maturation; mitochondrial respiration; gene ontology; retinoid x receptor; colony stimulating factor receptor; male; female; article; peroxisome proliferator activated receptor alpha; sialic acid binding immunoglobulin like lectin; macrophage culture; receptor type tyrosine protein phosphatase c; lipopolysaccharide binding protein; single cell rna seq; chromatin immunoprecipitation sequencing; pregnane x receptor; mh-s cell line |
| Journal Title: | Nature Communications |
| Volume: | 11 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-07-30 |
| Start Page: | 3822 |
| Language: | English |
| DOI: | 10.1038/s41467-020-17630-6 |
| PUBMED: | 32732898 |
| PROVIDER: | scopus |
| PMCID: | PMC7393351 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
