Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

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Space-time logic of liver gene expression at sub-lobular scale

Felix Naef, Clémence Yumie Syloun Hurni, Colas Noé Droin

The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive tempo ...

NATURE RESEARCH2021

Emerging functions of the nuclear receptor LRH-1 in liver physiology and pathology

Kristina Schoonjans, Hadrien Charles Edouard Demagny, Yu Sun

Nuclear receptors play pleiotropic roles in cell differentiation, development, proliferation, and metabolic processes to govern liver physiology and pathology. The nuclear receptor, liver receptor homolog-1 (LRH-1, NR5A2), originally identified in the live ...

2021

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

Xavier Fernandez-Real Girona

Background: The gut microbiome and iron status are known to play a role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. Results: Here, we applied an integrative systems medicine approa ...

2021

Circadian dynamics of RNA localisation in the mammalian liver

Clémence Yumie Syloun Hurni

Gene expression in eukaryotes is a complex multi-step process. It starts in the nucleus with transcription, the synthesis of a mRNA copy from a DNA template. While in the nucleus, the RNA transcript is subject to multiple co- and post-transcriptional modif ...

EPFL2021

SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

Bernard Schneider

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is considered a health epidemic with potential devastating effects on the patients and the healthcare systems. Current preclinical models of NAFLD are invariably imperfect and generally take a lon ...

2021

Assessment of Aspartate and Bicarbonate Produced From Hyperpolarized [1-13C]Pyruvate as Markers of Renal Gluconeogenesis

Arnaud Comment, Hikari Ananda Infinity Yoshihara

As both a consumer and producer of glucose, the kidney plays a significant role in glucose homeostasis. Measuring renal gluconeogenesis requires invasive techniques, and less invasive methods would allow renal gluconeogenesis to be measured more routinely. ...

2021

Transcriptomic analysis across liver diseases reveals disease-modulating activation of constitutive androstane receptor in cholestasis

Kristina Schoonjans, Jian Liu, Bhoomika Mathur

Background & Aims: Liver diseases are caused by many factors, such as genetics, nutrition, and viruses. Therefore, it is important to delineate transcriptomic changes that occur in various liver diseases. Methods: We performed high-throughput sequencing of ...

2020

TGR5/Cathepsin E signaling regulates macrophage innate immune activation in liver ischemia and reperfusion injury

Johan Auwerx, Kristina Schoonjans, Qi Wang

The role and underlying mechanism of plasma membrane-bound G protein-coupled bile acid receptor (TGR5) in regulating macrophage innate immune activation during liver ischemia and reperfusion (IR) injury remains largely unclear. Here, we demonstrated that T ...

2021

Compound 18 Improves Glucose Tolerance in a Hepatocyte TGR5-dependent Manner in Mice

Kristina Schoonjans, Adriano Maida

The bile acid receptor, TGR5, is a key regulator of glucose homeostasis, but the mechanisms by which TGR5 signaling improves glucose regulation are incompletely defined. In particular, TGR5 has an increasingly appreciated role in liver physiology and patho ...

2020

Mechano-modulatory synthetic niches for liver organoid derivation

Kristina Schoonjans, Matthias Lütolf, Giovanni Sorrentino, Saba Rezakhani, Ece Yildiz

The recent demonstration that primary cells from the liver can be expanded in vitro as organoids holds enormous promise for regenerative medicine and disease modelling. The use of three-dimensional (3D) cultures based on ill-defined and potentially immunog ...

Nature Publishing Group2020

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Transcriptomic analysis across liver diseases reveals disease-modulating activation of constitutive androstane receptor in cholestasis

Kristina Schoonjans, Jian Liu, Bhoomika Mathur

2020