期刊
CELL STEM CELL
卷 26, 期 5, 页码 657-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2020.01.017
关键词
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资金
- Institut National de la Sante et de la Recherche Medicale, France
- Centre National de la Recherche Scientifique, France
- Aix-Marseille University, France
- Agence Nationale de la Recherche, France [ANR-17-CE15-0007-01, ANR-18-CE120019-03]
- Fondation ARC pour la Recherche sur le Cancer, France [PGA1 RF20170205515]
- INSERM-Helmholtz cooperation
- European Research Council (ERC) [695093]
- Fondation ARC pour la Recherche sur le Cancer, France
- Berlin Institute of Health Einstein visiting fellow at MDC, Germany
- Alexander von Humboldt Professor at TU Dresden, Germany
- European Research Council (ERC) [695093] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-17-CE15-0007] Funding Source: Agence Nationale de la Recherche (ANR)
Hematopoietic stem cells (HSCs) maintain life-long production of immune cells and can directly respond to infection, but sustained effects on the immune response remain unclear. We show that acute immune stimulation with lipopolysaccharide (LPS) induced only transient changes in HSC abundance, composition, progeny, and gene expression, but persistent alterations in accessibility of specific myeloid lineage enhancers occurred, which increased responsiveness of associated immune genes to secondary stimulation. Functionally, this was associated with increased myelopoiesis of pre-exposed HSCs and improved innate immunity against the gram-negative bacterium P. aeruginosa. The accessible myeloid enhancers were enriched for C/EBP beta targets, and C/EBP beta deletion erased the long-term inscription of LPS-induced epigenetic marks and gene expression. Thus, short-term immune signaling can induce C/EBP beta-dependent chromatin accessibility, resulting in HSC-trained immunity, during secondary infection. This establishes a mechanism for how infection history can be epigenetically inscribed in HSCs as an integral memory function of innate immunity.
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