A5075079323- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Organ Transplantation Techniques and Outcomes
- Pancreatic function and diabetes
- Digestive system and related health
- Genetic and Kidney Cyst Diseases
- Liver Disease and Transplantation
- Drug Transport and Resistance Mechanisms
- Single-cell and spatial transcriptomics
- 3D Printing in Biomedical Research
- Epigenetics and DNA Methylation
- Gallbladder and Bile Duct Disorders
- Malaria Research and Control
- Pancreatitis Pathology and Treatment
- Cellular Mechanics and Interactions
- MicroRNA in disease regulation
- Growth Hormone and Insulin-like Growth Factors
- Pancreatic and Hepatic Oncology Research
- Renal and related cancers
- Cancer-related Molecular Pathways
- Congenital heart defects research
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
Karolinska Institutet
2019-2024
Agency for Science, Technology and Research
2015-2024
Charles University
2022
Institute of Molecular and Cell Biology
2015-2021
UCLouvain
2007-2019
National Cancer Centre Singapore
2018
KU Leuven
2005
Abstract Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding the spatial liver transcriptome in recent years. However, global differences across lobular units remain elusive physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis sectioned tissue. We confirm that this complex tissue is predominantly determined by zonation. By introducing novel computational approaches, enable gradient...
In chronic liver injury, progenitor cells (LPCs) proliferate in the periportal area, migrate inside lobule, and undergo further differentiation. This process is associated with extracellular matrix (ECM) remodeling. We analyzed LPC expansion accumulation a choline-deficient, ethionine-supplemented (CDE) model of proliferation. After day 3, CDE induced collagen deposits area. Expansion LPCs as assessed by increased number cytokeratin 19 (CK19)-positive was first observed at 7, while ECM...
Cell cycle regulation, especially faithful DNA replication and mitosis, are crucial to maintain genome stability. Cyclin-dependent kinase (CDK)/cyclin complexes drive most processes in cellular proliferation. In response damage, cell surveillance mechanisms enable normal cells arrest undergo repair processes. Perturbations genomic stability can lead tumor development suggest that regulators could be effective targets anticancer therapy. However, many clinical trials ended failure due...
The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter cell cycle and divide replace damaged cells. This capability is substantially reduced upon chronic damage, but it not clear if this cause or consequence disease. Here, we investigate whether blocking hepatocyte division using two different mouse models affects physiology as well clinical manifestations like fibrosis inflammation. We find that in P14 Cdk1Liv-/- mice, where abolished,...
Notch signaling promotes progenitor cell proliferation but inhibits hepatocyte differentiation during liver repair.
Upon infecting its vertebrate host, the malaria parasite initially invades liver where it undergoes massive replication, whilst remaining clinically silent. The coordination of host responses across complex tissue during infection remains unexplored. Here, we perform spatial transcriptomics in combination with single-nuclei RNA sequencing over multiple time points to delineate host-pathogen interactions Plasmodium berghei-infected tissues. Our data reveals significant changes gene expression...
Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes macrophages, peribiliary extracellular matrix (ECM) deposition ductular reaction (DR). This study aimed to elucidate the relevance macrophages in progression chronic cholangiopathies through macrophage depletion a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group mice...
Fibroblast growth factor 19 (FGF19) is produced in the small intestine and involved suppression of hepatic bile acid (BA) synthesis. FGF19 also expressed liver serum levels are elevated adults with cholestatic disease. This may reflect a rescue mechanism to dampen injury caused by increased intrahepatic BAs.To examine circulating at early stages biliary atresia short-term follow-up post-Kasai portoenterostomy (KPE) relation noncholestatic infants. The relationship between FGF19, BAs markers...
Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology visualize, digitalize, and segment two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof principle, we applied DUCT mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized intrahepatic bile duct paucity, that can...
Human hepatocytes are used for liver cell therapy, but the small number of engrafting cells limits benefit transplantation. We tested whether cotransplantation with hepatic stellate (HSCs) could improve hepatocyte engraftment in vivo. primary were transplanted into SCID mice either alone or a mixture HSCs (quiescent after culture activation) LX-2 (ratio 20:1). Four weeks transplantation mouse livers, human albumin-positive (huAlb + ) found scattered. When cotransplanted cells, huAlb formed...
The insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs/IGF2BPs) IMP1 and 3 are regarded as oncofetal proteins, whereas the hepatic IMP2 expression in adults is controversially discussed. splice variant IMP2-2/p62 promotes steatohepatitis hepatocellular carcinoma. Aim of this study was to clarify whether expressed adult liver influences progression toward cirrhosis. at higher levels embryonic compared tissues quantified embryonic, newborn, C57BL/6J mouse livers suggested by...
Abstract Background & Aims Alagille syndrome (ALGS) manifests with peripheral intrahepatic bile duct (IHBD) paucity, which can spontaneously resolve. In a model for ALGS, Jag1 Ndr/Ndr mice, this occurs distinct architectural mechanisms in hilar and IHBDs. Here, we investigated region‐specific IHBD characteristics addressed whether IGF1, cholangiocyte mitogen that is downregulated ALGS improve biliary outcomes. Methods Intrahepatic organoids (ICOs) were derived from adult +/+ livers...