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C/EBPβ-dependent epigenetic memory induces trained immunity in hematopoietic stem cells

Item Type:Article
Title:C/EBPβ-dependent epigenetic memory induces trained immunity in hematopoietic stem cells
Creators Name:de Laval, B. and Maurizio, J. and Kandalla, P.K. and Brisou, G. and Simonnet, L. and Huber, C. and Gimenez, G. and Matcovitch-Natan, O. and Reinhardt, S. and David, E. and Mildner, A. and Leutz, A. and Nadel, B. and Bordi, C. and Amit, I. and Sarrazin, S. and Sieweke, M.H.
Abstract: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 HSC and improved innate immunity against the gram-negative bacterium P. aeruginosa. The accessible myeloid enhancers were enriched for C/EBPβ (targets, and C/EBPβ deletion erased the long-term inscription of LPS-induced epigenetic marks and gene expression. Thus, short-term immune signaling can induce C/EBPβ-dependent chromatin accessibility, resulting in HSC-trained immunity, during secondary infection. This establishes a mechanism for how infection history can be epigenetically inscribed in HSC as an integral memory function of innate immunity.
Keywords:HSC, Epigenetic Memory, Trained Immunity, Innate Immune Response, C/EBPβ
Source:Cell Stem Cell
Publisher:Cell Press
Page Range:657-674
Date:May 2020
Additional Information:Erratum in: Cell Stem Cell 26(5): 793. Erratum in: Cell Stem Cell 30(1): 112.
Official Publication:https://doi.org/10.1016/j.stem.2020.01.017
PubMed:View item in PubMed

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