Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis

Ramachandran, Prakash; Matchett, Kylie P.; Dobie, Ross; Wilson-Kanamori, John; Henderson, Neil C.

doi:10.1038/s41575-020-0304-x

Cited by 176 publications

(156 citation statements)

References 174 publications

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“…Indeed, while murine KCs are mainly identified as F4/80 + CD11b int Clec4F + cells, 58,59 single-cell RNA-sequencing data has defined the human KC population as CD163 + MARCO + CD5L + TIMD4 + . 60 Interestingly, a subpopulation of TREM2 + macrophages was found in the fibrotic scars of human cirrhotic livers by single-cell RNAsequencing and immunohistochemical studies. 61 A comprehensive analysis of early macrophage development during human embryogenesis suggested that yolk sac-derived primitive macrophages or embryonic liver monocytes as the major sources of tissue-resident macrophages in humans.…”

Section: Hepatic Macrophages In Liver Diseasesmentioning

confidence: 98%

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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Macrophages, which are key cellular components of the liver, have emerged as essential players in the maintenance of hepatic homeostasis and in injury and repair processes in acute and chronic liver diseases. Upon liver injury, resident Kupffer cells (KCs) sense disturbances in homeostasis, interact with hepatic cell populations and release chemokines to recruit circulating leukocytes, including monocytes, which subsequently differentiate into monocyte-derived macrophages (MoMϕs) in the liver. Both KCs and MoMϕs contribute to both the progression and resolution of tissue inflammation and injury in various liver diseases. The diversity of hepatic macrophage subsets and their plasticity explain their different functional responses in distinct liver diseases. In this review, we highlight novel findings regarding the origins and functions of hepatic macrophages and discuss the potential of targeting macrophages as a therapeutic strategy for liver disease.

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Section: Hepatic Macrophages In Liver Diseasesmentioning

confidence: 98%

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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“…Single-cell genomics allows the unbiased exploration of cell states and cell types at single-cell resolution, leading to a revolutionary change in our understanding of liver biology and disease pathogenesis [16]. However, single-cell RNA-seq (scRNA-seq) in the liver is associated with some caveats.…”

Section: Discussionmentioning

confidence: 99%

“…All these cells are organized in repetitive structures named liver lobules [8,9]. The analysis of individual cells by single-cell genomics is changing our understanding of liver homeostasis and pathogenic conditions by taking into account their spatial distribution [10][11][12][13][14][15][16]. However, single-cell isolations from the liver require harsh enzymatic or mechanical dissociation protocols that perturb the mRNA levels [17].…”

Section: Introductionmentioning

confidence: 99%

“Single-nucleus RNA-seq2 reveals a functional crosstalk between liver zonation and ploidy”

Richter

Deligiannis

Danese

et al. 2020

Preprint

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Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity we have developed a single-nucleus RNA-seq-2 method that allows deep characterization of nuclei isolated from frozen archived tissues. We have used this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobe. Our work has revealed a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.

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“…Consequently, it is likely that the observed mutations and alterations in gene expression relate to DNA derived from HCC cells. The application of single-cell transcriptome analysis will help to resolve the liver cell types responsible for altered gene expression in HCC [ 76 ].…”

Section: Mutations and Altered Expression Of Ca 2+mentioning

confidence: 99%

Targeting Ca2+ Signaling in the Initiation, Promotion and Progression of Hepatocellular Carcinoma

Ali

Rychkov

Barritt

2020

Cancers

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Hepatocellular carcinoma (HCC) is a considerable health burden worldwide and a major contributor to cancer-related deaths. HCC is often not noticed until at an advanced stage where treatment options are limited and current systemic drugs can usually only prolong survival for a short time. Understanding the biology and pathology of HCC is a challenge, due to the cellular and anatomic complexities of the liver. While not yet fully understood, liver cancer stem cells play a central role in the initiation and progression of HCC and in resistance to drugs. There are approximately twenty Ca2+-signaling proteins identified as potential targets for therapeutic treatment at different stages of HCC. These potential targets include inhibition of the self-renewal properties of liver cancer stem cells; HCC initiation and promotion by hepatitis B and C and non-alcoholic fatty liver disease (principally involving reduction of reactive oxygen species); and cell proliferation, tumor growth, migration and metastasis. A few of these Ca2+-signaling pathways have been identified as targets for natural products previously known to reduce HCC. Promising Ca2+-signaling targets include voltage-operated Ca2+ channel proteins (liver cancer stem cells), inositol trisphosphate receptors, store-operated Ca2+ entry, TRP channels, sarco/endoplasmic reticulum (Ca2++Mg2+) ATP-ase and Ca2+/calmodulin-dependent protein kinases. However, none of these Ca2+-signaling targets has been seriously studied any further than laboratory research experiments. The future application of more systematic studies, including genomics, gene expression (RNA-seq), and improved knowledge of the fundamental biology and pathology of HCC will likely reveal new Ca2+-signaling protein targets and consolidate priorities for those already identified.

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Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis

Cited by 176 publications

References 174 publications

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

“Single-nucleus RNA-seq2 reveals a functional crosstalk between liver zonation and ploidy”

Targeting Ca2+ Signaling in the Initiation, Promotion and Progression of Hepatocellular Carcinoma

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