Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(12), P. 1596 - 1607

Published: Dec. 20, 2021

Language: Английский

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Hepatic stellate cells in physiology and pathology

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 600(8), P. 1825 - 1837

Published: March 21, 2022

Hepatic stellate cells (HSCs) comprise a minor cell population in the liver but serve numerous critical functions normal and response to injury. HSCs are primarily known for their activation upon injury producing collagen-rich extracellular matrix fibrosis. In absence of injury, reside quiescent state, which main function appears be storage retinoids or vitamin A-containing metabolites. Less appreciated include amplifying hepatic inflammatory expressing growth factors that development both initiation termination regeneration. Recent single-cell RNA sequencing studies have corroborated earlier indictaing HSC involves diverse array phenotypic alterations identified unique populations. This review serves highlight these many HSCs, briefly describe recent genetic tools will help thoroughly investigate role physiology pathology.

Language: Английский

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Polygenic enrichment distinguishes disease associations of individual cells in single-cell RNA-seq data

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(10), P. 1572 - 1580

Published: Sept. 1, 2022

Language: Английский

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Liver zonation, revisited

Hepatology, Journal Year: 2022, Volume and Issue: 76(4), P. 1219 - 1230

Published: Feb. 17, 2022

Abstract The concept of hepatocyte functional zonation is well established, with differences in metabolism and xenobiotic processing determined by multiple factors including oxygen nutrient levels across the hepatic lobule. However, recent advances single‐cell genomics technologies, nuclei RNA sequencing, rapidly evolving fields spatial transcriptomic proteomic profiling have greatly increased our understanding liver zonation. Here we discuss how these transformative experimental strategies are being leveraged to dissect at unprecedented resolution this new information should facilitate emergence novel precision medicine‐based therapies for patients disease.

Language: Английский

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Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116702 - 116702

Published: May 11, 2024

In recent years, nanoparticles have been broadly utilized in various drugs delivery formulations. Nanodelivery systems shown promise solving problems associated with the distribution of hydrophobic and promoted accumulation nanomedicines circulation or organs. However, injection dose (NPs) is much greater than that needed by diseased tissues other words, most NPs are localized off-target do not reach desired tissue With rapid development biodegradable biosafety nanomaterials, nanovectors represent assurance safety. effects also induce concerns about application NPs, especially gene editing tools. Therefore, a complete understanding biological responses to body will clearly guide design targeted NPs. The different properties nanodelivery may diverse interactions between carriers this review, we describe relationship liver, influenced organ systemic administration nanoplatforms. Various transport vehicles adopted multiple strategies for cells homeostasis liver liver. Additionally, provide novel strategy treating incurable diseases. appearance has profoundly improved

Language: Английский

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In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(785)

Published: Feb. 12, 2025

Homology-directed repair (HDR)–based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility limited by inefficient and imprecise DNA mechanisms in terminally differentiated tissues. Here, we tested Repair Drive, platform technology for selectively expanding HDR-corrected hepatocytes adult mice vivo. Drive involves transient conditioning the liver knocking down essential gene, fumarylacetoacetate hydrolase ( Fah ), delivering untargetable version gene cis with therapeutic transgene. We show increased percentage correctly targeted healthy wild-type up to 25%, which resulted fivefold expression transgene, human factor IX FIX ). was well tolerated did not induce toxicity or tumorigenesis during 1-year follow-up. This may broaden diseases can be treated somatic editing.

Language: Английский

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Why Do Lipid Nanoparticles Target the Liver? Understanding of Biodistribution and Liver-Specific Tropism

Molecular Therapy — Methods & Clinical Development, Journal Year: 2025, Volume and Issue: 33(1), P. 101436 - 101436

Published: Feb. 16, 2025

Lipid nanoparticles (LNPs) are now highly effective transporters of nucleic acids to the liver. This liver-specificity is largely due their association with certain serum proteins, most notably apolipoprotein E (ApoE), which directs them liver cells by binding low-density lipoprotein (LDL) receptors on hepatocytes. The liver's distinct anatomy, its various specialized cell types, also influences how LNPs taken up from circulation, cleared, and they in delivering treatments. In this review, we consider factors that facilitate LNP's targeting explore latest advances liver-targeted LNP technologies. Understanding targeted can help for design optimization nanoparticle-based therapies. Comprehension cellular interaction biodistribution not only leads better treatments diseases but delivers insight directing other tissues, potentially broadening range therapeutic applications.

Language: Английский

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Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis

Annual Review of Nutrition, Journal Year: 2022, Volume and Issue: 42(1), P. 91 - 113

Published: May 19, 2022

Nonalcoholic fatty liver disease (NAFLD), a spectrum of metabolic associated with obesity, ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis (NASH). The latter is characterized by persistent injury, inflammation, and fibrosis, which collectively increase the risk for end-stage diseases such as cirrhosis hepatocellular carcinoma. Recent work has shed new light on pathophysiology NAFLD/NASH, particularly role genetic, epigenetic, dietary factors dysfunctions in other tissues driving excess fat accumulation injury. In parallel, single-cell RNA sequencing studies have revealed unprecedented details molecular nature cell heterogeneity, intrahepatic cross talk, disease-associated reprogramming immune stromal vascular microenvironment. This review covers recent advances these areas, emerging concepts NASH pathogenesis, potential therapeutic opportunities.

Language: Английский

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Single‐cell transcriptomics reveals conserved cell identities and fibrogenic phenotypes in zebrafish and human liver

Hepatology Communications, Journal Year: 2022, Volume and Issue: 6(7), P. 1711 - 1724

Published: March 22, 2022

Abstract The mechanisms underlying liver fibrosis are multifaceted and remain elusive with no approved antifibrotic treatments available. adult zebrafish has been an underutilized tool to study fibrosis. We aimed characterize the single‐cell transcriptome of determine its utility as a model for studying used RNA sequencing (scRNA‐seq) molecular cellular dynamics at level. performed comparative analysis scRNA‐seq human focus on hepatic stellate cells (HSCs), driver in reveals transcriptionally unique populations cell types that comprise liver. Joint clustering data demonstrates high conservation transcriptional profiles marker genes zebrafish. Human HSCs show profiles, we uncover collectin subfamily member 11 ( colec11 ) novel, conserved HSCs. To demonstrate power using zebrafish, our pediatric disease mutation mannose phosphate isomerase MPI characteristic early found signaling pathways upstream regulators across MPI‐depleted CellPhoneDB identified neuropilin 1 potential Conclusion: This establishes first atlas liver, highlights degree similarity strengthens value

Language: Английский

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Absolute scaling of single-cell transcriptomes identifies pervasive hypertranscription in adult stem and progenitor cells

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111978 - 111978

Published: Jan. 1, 2023

Hypertranscription supports biosynthetically demanding cellular states through global transcriptome upregulation. Despite its potential widespread relevance, documented examples of hypertranscription remain few and limited to early development. Here, we demonstrate that absolute scaling single-cell RNA-sequencing data enables the estimation total transcript abundances per cell. We validate in known cases developmental apply it adult cell types, revealing a remarkable dynamic range transcriptional output. In organs, marks activated stem/progenitor cells with multilineage is redeployed conditions tissue injury, where precedes bursts proliferation during regeneration. Our analyses identify common set molecular pathways associated both embryonic hypertranscription, including chromatin remodeling, DNA repair, ribosome biogenesis, translation. These shared features across diverse contexts support as general program pervasively employed development, organ maintenance,

Language: Английский

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