A5030754446- Social and Educational Sciences
- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Research in Social Sciences
- Gallbladder and Bile Duct Disorders
- Pluripotent Stem Cells Research
- Liver Disease Diagnosis and Treatment
- Developmental Biology and Gene Regulation
- Nuclear Receptors and Signaling
- Organ Transplantation Techniques and Outcomes
- MicroRNA in disease regulation
- Education, Healthcare and Sociology Research
- Genetic and Kidney Cyst Diseases
- Genetics and Neurodevelopmental Disorders
- Early Childhood Education and Development
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- Congenital Anomalies and Fetal Surgery
- Complex Systems and Decision Making
- Pancreatic and Hepatic Oncology Research
- RNA Research and Splicing
- Digestive system and related health
- Single-cell and spatial transcriptomics
- Education and Critical Thinking Development
- interferon and immune responses
Karolinska Institutet
2013-2024
American Civil Liberties Union
2019
Stockholm South General Hospital
2017
Karolinska University Hospital
1991-2013
KTH Royal Institute of Technology
2009
Masaryk University
2008
Yonsei University
2008
NOAA National Weather Service
2005
National Institute of Meteorology
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...
Notch signaling is frequently hyperactivated in breast cancer, but how the enhanced contributes to tumor process less well understood. In this report, we identify proinflammatory cytokine interleukin-6 (IL-6) as a novel target cells. Enhanced upregulated IL-6 expression, leading activation of autocrine and paracrine Janus kinase/signal transducers activators transcription signaling. upregulation was mediated by non-canonical signaling, it could be effectuated cytoplasmically localized...
Wnts are a family of secreted proteins that regulate multiple steps neural development and stem cell differentiation. Two them, Wnt1 Wnt5a, activate distinct branches Wnt signaling individually different aspects midbrain dopaminergic (DA) neuron development. However, several their functions interactions remain to be elucidated. Here, we report loss results in Lmx1a Ngn2 expression, as well agenesis DA neurons the floor plate. Remarkably, few ectopic still emerge basal plate Wnt1(-/-) mice,...
Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes Notch ligand, although it not clear how these contribute to disease development. We aimed develop mouse model of elucidate mechanisms.Mice missense mutation (H268Q) Jag1 (Jag1+/Ndr mice) were outbred C3H/C57bl6 background generate for (Jag1Ndr/Ndr mice)....
Notch signaling controls multiple aspects of embryonic development and adult homeostasis. Alagille syndrome is usually caused by a single mutation in the jagged canonical ligand 1 (JAG1), manifests with liver disease cardiovascular symptoms that are direct consequence JAG1 haploinsufficiency. Recent insights into Jag1/Notch-controlled developmental homeostatic processes explain how pathology develops hepatic systems and, together recent elucidation mechanisms modulating regeneration, provide...
Lrp5/6 are crucial coreceptors for Wnt/β-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of in signaling. We found that Lrp6 physically interacts with Wnt5a, but this does not lead to phosphorylation or activation pathway. Overexpression blocks Wnt5a downstream target Rac1, and effect is dependent on intact extracellular domains. These results suggested domain inhibits vitro. In vivo, Lrp6−/− mice...
Wnt5a is a morphogen that activates the Wnt/planar cell polarity (PCP) pathway and serves multiple functions during development. PCP signaling controls orientation of cells within an epithelial plane as well convergent extension (CE) movements. was previously reported to promote differentiation A9-10 dopaminergic (DA) precursors in vitro. However, mechanism DA function midbrain development vivo remains unclear. We hereby report activated GTPase Rac1 inhibitors blocked Wnt5a-induced neuron...
In Notch signaling, cell-bound ligands activate receptors on juxtaposed cells, but the relationship between ligand endocytosis, ubiquitylation and ligand-receptor interaction remains poorly understood. To study specific role of interaction, we identified a missense mutant Jagged1 (Nodder, Ndr) that failed to interact with receptors, retained cellular distribution was similar wild-type (Jagged1(WT)) in absence active signaling. Both Jagged1(WT) Jagged1(Ndr) interacted E3 ubiquitin ligase Mind...
In this study, we examined the signaling pathways activated by Wnt5a in endothelial differentiation of embryonic stem (ES) cells and function during vascular development. We first found that Wnt5a(-/-) mouse (mES) exhibited a defect differentiation, which was rescued addition Wnt5a, suggesting is required for ES cells. Involvement both beta-catenin protein kinase (PK)Calpha mES requiring indicated activation PKCalpha Wnt5a(+/-) but not also or knockdowns inhibited Wnt5a-induced Moreover,...
Secreted Frizzled related proteins (sFRPs) are a family of that modulate Wnt signaling, which in turn regulates multiple aspects ventral midbrain (VM) and dopamine (DA) neuron development. However, it is not known signaling branch what DA development regulated by sFRPs. Here, we show sFRP1 sFRP2 activate the Wnt/planar‐cell‐polarity/Rac1 pathway cells. In developing VM, expressed at low levels, sFRP1−/− or sFRP2−/− mice had no detectable phenotype. compound sFRP1−/−;sFRP2−/− mutants revealed...
Embryonic neural stem cells (NSCs), comprising neuroepithelial and radial glial cells, are indispensable precursors of neurons glia in the mammalian developing brain. Since process neurogenesis occurs a hypoxic environment, question arises how NSCs deal with low oxygen tension whether it affects their stemness. Genes from hypoxia-inducible factors (HIF) family well known governing cellular response to conditions. In this study, we have discovered that endogenous stabilization factor 1α...