Liver-Derived Signals Sequentially Reprogram Myeloid Enhancers to Initiate and Maintain Kupffer Cell Identity

Sakai, Mashito; Troutman, Ty Dale; Seidman, Jason S.; Ouyang, Zhengyu; Spann, Nathanael J.; Abe, Yohei; Ego, Kaori M.; Bruni, Cassi M.; Deng, Zongwu; Schlachetzki, J; Nott, Alexi; Bennett, Hunter; Chang, Jonathan; Vu, Bao Chau T.; Pasillas, Martina P.; Link, Verena M.; Texari, Lorane; Heinz, Sven; Thompson, Bonne M.; McDonald, Jeffrey G.; Geissmann, Frédéric; Glass, Christopher K.

doi:10.1016/j.immuni.2019.09.002

Cited by 252 publications

(265 citation statements)

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“…Thus, tissue niche is arguably the most important driver of resident macrophage function. However, the cellular and molecular pathways that program the resident macrophage identity are just beginning to be understood (3,4). Although tissue resident macrophages share common functions, including tissue remodeling and clearance of cellular debris, they can also exert specific tissue function.…”

Section: Introductionmentioning

confidence: 99%

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

Daemen

Schilling

2020

Front. Immunol.

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Obesity is associated with the development of metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. The presence of chronic, low-grade inflammation appears to be an important mechanistic link between excess nutrients and clinical disease. The onset of these metabolic disorders coincides with changes in the number and phenotype of macrophages in peripheral organs, particularly in the liver and adipose tissue. Macrophage accumulation in these tissues has been implicated in tissue inflammation and fibrosis, contributing to metabolic disease progression. Recently, the concept has emerged that changes in macrophage metabolism affects their functional phenotype, possibly triggered by distinct environmental metabolic cues. This may be of particular importance in the setting of obesity, where both liver and adipose tissue are faced with a high metabolic burden. In the first part of this review we will discuss current knowledge regarding macrophage dynamics in both adipose tissue and liver in obesity. Then in the second part, we will highlight data linking macrophage metabolism to functional phenotype with an emphasis on macrophage activation in metabolic disease. The importance of understanding how tissue niche influences macrophage function in obesity will be highlighted. In addition, we will identify important knowledge gaps and outstanding questions that are relevant for future research in this area and will facilitate the identification of novel targets for therapeutic intervention in associated metabolic diseases.

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Section: Introductionmentioning

confidence: 99%

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

Daemen

Schilling

2020

Front. Immunol.

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“…LSEC-to-monocyte interactions are crucial in determining the fate of circulating monocytes and their differentiation into liver macrophages. 43 Livers of Kupffer cell (KC)-depleted mice are rapidly repopulated by circulating monocytes which acquire a KC-like phenotype. LSECs express DLL4 (delta like canonical Notch ligand 4) and TGFβ1 (transforming growth factor β1) that interact, respectively, with NOTCH and TGFβ/BMP receptors on monocytes, downregulating monocyte-specific genes.…”

Section: Novel Insights Into Chronic Liver Disease and Cancer Microenmentioning

confidence: 99%

Single-cell genomics and spatial transcriptomics: Discovery of novel cell states and cellular interactions in liver physiology and disease biology

Saviano

Henderson

Baumert

2020

Journal of Hepatology

162

110

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Summary Transcriptome analysis enables the study of gene expression in human tissues and is a valuable tool to characterise liver function and gene expression dynamics during liver disease, as well as to identify prognostic markers or signatures, and to facilitate discovery of new therapeutic targets. In contrast to whole tissue RNA sequencing analysis, single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics enables the study of transcriptional activity at the single cell or spatial level. ScRNA-seq has paved the way for the discovery of previously unknown cell types and subtypes in normal and diseased liver, facilitating the study of rare cells (such as liver progenitor cells) and the functional roles of non-parenchymal cells in chronic liver disease and cancer. By adding spatial information to scRNA-seq data, spatial transcriptomics has transformed our understanding of tissue functional organisation and cell-to-cell interactions in situ. These approaches have recently been applied to investigate liver regeneration, organisation and function of hepatocytes and non-parenchymal cells, and to profile the single cell landscape of chronic liver diseases and cancer. Herein, we review the principles and technologies behind scRNA-seq and spatial transcriptomic approaches, highlighting the recent discoveries and novel insights these methodologies have yielded in both liver physiology and disease biology.

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“…Basically, two main sources of macrophages were identified, namely, tissue-resident macrophages and circulatingderived macrophages. Tissue-resident macrophages exhibit a distinct phenotype that is linked to the corresponding functions of corresponding tissue, such as Clec4f + Kupffer cells (KCs) (liver-resident macrophages) in the liver [8]. In addition, macrophages were originally proposed to be derived from circulating monocytes.…”

Section: Previous Perspectivementioning

confidence: 99%

Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future

Wang

Gong

et al. 2020

Mediators of Inflammation

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The ontogeny of macrophages in most organs has already been established. Owing to the limited number and inaccessibility of synovial macrophages (SMs), the origin of SMs has not been fully elucidated. Previous studies suggested that SMs have two major origins, namely, tissue-resident and monocyte-derived SMs. However, no systematic analysis to identify SM ontology in either physiological or pathological conditions has been available to date. In this review, we summarize relevant studies on the two main origins of SMs in rheumatoid arthritis (RA) and forecast the future research directions for this field. Furthermore, we discuss the current state of RA therapy that is based on targeting different SM subsets.

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Liver-Derived Signals Sequentially Reprogram Myeloid Enhancers to Initiate and Maintain Kupffer Cell Identity

Cited by 252 publications

References 50 publications

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

Single-cell genomics and spatial transcriptomics: Discovery of novel cell states and cellular interactions in liver physiology and disease biology

Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future

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