Regulation of pDC Fate Determination by Histone Deacetylase 3
- Tsinghua University, China
Abstract
Dendritic cells (DCs), the key antigen-presenting cells, are primary regulators of immune responses. Transcriptional regulation of DC development had been one of the major research interests in DC biology, however, the epigenetic regulatory mechanisms during DC development remains unclear. Here, we report that Histone deacetylase 3 (Hdac3), an important epigenetic regulator, is highly expressed in pDCs, and its deficiency profoundly impaired the development of pDCs. Significant disturbance of homeostasis of hematopoietic progenitors was also observed in HDAC3-deficient mice, manifested by altered cell numbers of these progenitors and defective differentiation potentials for pDCs. Using the in vitro Flt3L supplemented DC culture system, we further demonstrated that HDAC3 was required for the differentiation of pDCs from progenitors at all developmental stages. Mechanistically, HDAC3 deficiency resulted in enhanced expression of cDC1-associated genes, owing to markedly elevated H3K27 acetylation (H3K27ac) at these gene sites in BM pDCs. In contrast, the expression of pDC-associated genes was significantly downregulated, leading to defective pDC differentiation.
Data availability
For original data, please contact wuli@mail.tsinghua.edu.cnRNA sequencing data are available at NCBI GEO Datasets under accession GSE197207, methods were described. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197207Cut & Tag data are available at NCBI GEO Datasets under accession GSE197212, methods were described. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197212
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Genome-wide maps of H3K27ac in HDAC3 knockout bone marrow pDCs compared with control pDCsNCBI Gene Expression Omnibus, GSE197212.
Article and author information
Author details
Funding
Ministry of Science and Technology of the People's Republic of China (National Key Research Project 2019YFA0508502)
- Li Wu
National Natural Science Foundation of China (31991174)
- Li Wu
National Natural Science Foundation of China (31800769)
- Zhimin He
Center for Life Sciences
- Li Wu
Ministry of Science and Technology of the People's Republic of China (National Key Research Project 2022YFC2505001)
- Li Wu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Satyajit Rath, Indian Institute of Science Education and Research (IISER), India
Ethics
Animal experimentation: All animal procedures were performed in strict accordance with the recommendations and approval of the Institutional Animal Care and Use Committee of Tsinghua University, protocol permit number: 18-WL2.
Version history
- Received: May 22, 2022
- Preprint posted: June 10, 2022 (view preprint)
- Accepted: November 22, 2023
- Accepted Manuscript published: November 27, 2023 (version 1)
- Version of Record published: December 20, 2023 (version 2)
- Version of Record updated: December 29, 2023 (version 3)
- Version of Record updated: January 8, 2024 (version 4)
Copyright
© 2023, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Regulation of pDC Fate Determination by Histone Deacetylase 3
eLife 12:e80477.
https://doi.org/10.7554/eLife.80477
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