Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming

Aguilar-Bravo, Beatriz; Ariño, Sílvia; Blaya, Delia; Pose, Elisa; Torre, Raquel A Martinez García de la; Latasa, María U.; Martínez-Sánchez, Celia; Zanatto, Laura; Sererols-Viñas, Laura; Cantallops-Vilà, Paula; Affò, Silvia; Coll, Mar; Thillen, Xavier; Dubuquoy, Laurent; Ávila, Matías A.; Argemí, Josepmaria; Paz, Arantza Lamas; Nevzorova, Yulia A.; Cubero, Francisco Javier; Bataller, Ramón; Lozano, Juan José; Ginès, Pere; Sancho‐Bru, Pau

doi:10.1016/j.jhep.2023.04.013

Cited by 12 publications

(6 citation statements)

References 38 publications

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“… 46 In addition, studies have reported that overexpression of CXCR4 in the liver in chronic liver injury decreases the expression of hepatocyte-specific genes and promotes liver injury. 47 …”

Section: Discussionmentioning

confidence: 99%

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD

Bai,

Zhu,

et al. 2023

Hepatology Communications

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Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease prevalent worldwide, with an increasing incidence associated with obesity, diabetes, and metabolic syndrome. The progression of MASLD to metabolic dysfunction–associated steatohepatitis (MASH) poses a pressing health concern, highlighting the significance of accurately identifying MASLD and its progression to MASH as a primary challenge in the field. In this study, a systematic integration of 66 immune cell types was conducted. Comprehensive analyses were performed on bulk, single-cell RNA-Seq, and clinical data to investigate the immune cell types implicated in MASLD progression thoroughly. Multiple approaches, including immune infiltration, gene expression trend analysis, weighted gene coexpression network analysis, and 4 machine learning algorithms, were used to examine the dynamic changes in genes and immune cells during MASLD progression. C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 have been identified as potential diagnostic biomarkers for MASLD progression. Furthermore, cell communication analysis at the single-cell level revealed that the involvement of C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 in MASLD progression is mediated through their influence on T cells. Overall, our study identified vital immune cells and a 2-gene diagnostic signature for the progression of MASLD, providing a new perspective on the diagnosis and immune-related molecular mechanisms of MASLD. These findings have important implications for developing innovative diagnostic tools and therapies for MASLD.

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Section: Discussionmentioning

confidence: 99%

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD

Bai,

Zhu,

et al. 2023

Hepatology Communications

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“…Thus, targeting DR to preferentially differentiate hepatic progenitor cells into hepatocytes is a potential strategy for the treatment of advanced ALD. Several drivers of DR have been identified, including modulation of biliary NF-κB activity, long noncoding RNA ACTA2-AS1, mTOR activation, CXCR4-mediated hepatocyte dedifferentiation, and neutrophil or macrophage infiltration (67)(68)(69)(70)(71)(72)(73)(74)(75)(76). Of these, inflammation-mediated DR, mTOR activation, and biliary NF-κB activity alterations seem to be present in human ALD samples, indicating their translational significance.…”

Section: Application Of Cutting-edge Technologies In Aldmentioning

confidence: 99%

Alcohol-associated liver disease

Mackowiak,

Fu,

Maccioni

et al. 2024

Journal of Clinical Investigation

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“…Invasive DRs lead to the formation of disorganized tubular structures with poorly defined ductular lumens, which affect the tissue architecture [72]. In humans, invasive DRs were observed in patients with chronic cholestatic liver diseases, nonalcoholic fatty liver disease, alcoholic liver disease, and viral hepatitis C [73][74][75][76][77][78] and in rodent models that were subjected to a choline-deficient diet or thioacetamide administration [79][80][81][82]. In metabolic syndrome, DRs are induced by systemic inflammation triggered by senescent hepatocytes, whereas in hepatitis C infections, insulin resistance and inflammation are the key factors that drive the induction of DRs [77].…”

Section: Types Of Ductular Reactionsmentioning

confidence: 99%

Ductular Reactions in Liver Injury, Regeneration, and Disease Progression—An Overview

Mavila,

Siraganahalli Eshwaraiah,

Kennedy

2024

Cells

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Ductular reaction (DR) is a complex cellular response that occurs in the liver during chronic injuries. DR mainly consists of hyper-proliferative or reactive cholangiocytes and, to a lesser extent, de-differentiated hepatocytes and liver progenitors presenting a close spatial interaction with periportal mesenchyme and immune cells. The underlying pathology of DRs leads to extensive tissue remodeling in chronic liver diseases. DR initiates as a tissue-regeneration mechanism in the liver; however, its close association with progressive fibrosis and inflammation in many chronic liver diseases makes it a more complicated pathological response than a simple regenerative process. An in-depth understanding of the cellular physiology of DRs and their contribution to tissue repair, inflammation, and progressive fibrosis can help scientists develop cell-type specific targeted therapies to manage liver fibrosis and chronic liver diseases effectively.

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Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming

Cited by 12 publications

References 38 publications

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD

Alcohol-associated liver disease

Ductular Reactions in Liver Injury, Regeneration, and Disease Progression—An Overview

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