A5012198620- Neurogenesis and neuroplasticity mechanisms
- Neonatal Respiratory Health Research
- MicroRNA in disease regulation
- Congenital Diaphragmatic Hernia Studies
- Platelet Disorders and Treatments
- Barrier Structure and Function Studies
- Venous Thromboembolism Diagnosis and Management
- Mesenchymal stem cell research
- Cardiac tumors and thrombi
- Fibroblast Growth Factor Research
- Single-cell and spatial transcriptomics
- Angiogenesis and VEGF in Cancer
- Pulmonary Hypertension Research and Treatments
- Kruppel-like factors research
- Congenital heart defects research
- Cerebrospinal fluid and hydrocephalus
- Fetal and Pediatric Neurological Disorders
- Inflammatory Biomarkers in Disease Prognosis
- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Acute Ischemic Stroke Management
- Neonatal and fetal brain pathology
- Renal Diseases and Glomerulopathies
Uppsala University
2013-2023
Karolinska Institutet
2004-2012
Ludwig Cancer Research
2008-2011
Karolinska University Hospital
2008
Ludwig Cancer Research
2008
Abstract Vascular diseases are major causes of death, yet our understanding the cellular constituents blood vessels, including how differences in their gene expression profiles create diversity vascular structure and function, is limited. In this paper, we describe a single-cell RNA sequencing (scRNA-seq) dataset that defines vessel-associated cell types subtypes mouse brain lung. The contains 3,436 single transcriptomes from brain, which formed 15 distinct clusters corresponding to...
Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment barrier enclosure brain. The exact nature leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically cell types pia, inner outer arachnoid barrier, dural border layer; contrast sixth transcriptome present choroid plexus median eminence. Newly identified transcriptional markers...
Abstract Cancer results from the concerted performance of malignant cells and stromal cells. Cell types populating microenvironment are enlisted by tumor to secrete a host growth-promoting cues, thus upholding initiation progression. Platelet-derived growth factors (PDGF) support formation prominent compartment as yet unidentified molecular effectors. Whereas PDGF-CC induces fibroblast reactivity fibrosis in range tissues, little is known about function shaping tumor-stroma interplay....
The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded completion....
Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) contribute to normal heart development. Deficient or abnormal expression of Pdgf Pdgfr genes have a negative impact on cardiac development function. The cellular effects PDGFs in the hearts Pdgf/Pdgfr mutants pathogenesis resulting abnormalities are poorly understood, but different PDGF isoforms induce varying effects. Here, we generated three new transgenic mouse types which complete set studies, where all ligands been...
Abstract Meninges cover the surface of brain and spinal cord contribute to protection immune surveillance central nervous system (CNS). How meningeal layers establish CNS compartments with different accessibility cells mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions arachnoid pia mater that form leptomeninges border subarachnoid space (SAS) filled cerebrospinal fluid (CSF)....
Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor β-positive pericytes to blood vessels. The endothelium is an essential source PDGFB this process. Platelets constitute major reservoir and are continuously activated the tumor microenvironment, exposing tumors plethora factors contained platelet granules. Here, we show that vascular function, as well pericyte coverage significantly impaired mice with conditional knockout platelets. A lack platelets...
Oligodendrocyte progenitor cells (OPCs) are widely distributed of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities adulthood contribute to oligodendrogenesis myelin turnover; however, the regulatory mechanisms their cell dynamics largely remain unknown. Here, we found global Pdgfra inactivation mice rapidly led elimination OPCs due synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by active...
The development of neuronal networks in the brain requires differentiation functional synapses. Neurobeachin (Nbea) was identified as a putative regulator membrane protein trafficking associated with tubulovesicular endomembranes and postsynaptic plasma membranes. Nbea is essential for evoked transmission at neuromuscular junctions, but its role central nervous system has not been characterized. Here, we have studied synapses newly generated gene-trap knockout (KO) mouse line embryonic day...
ABSTRACT Platelet-derived growth factor A (PDGF-A) signaling through PDGF receptor α is essential for alveogenesis. Previous studies have shown that Pdgfa−/− mouse lungs enlarged alveolar airspace with absence of secondary septation, both distinctive features bronchopulmonary dysplasia. To study how PDGF-A involved in alveogenesis, we generated lung-specific Pdgfa knockout mice (Pdgfafl/−; Spc-cre) and characterized their phenotype postnatally. Histological differences between mutant...
Abstract Glioblastomas are the most common and malignant astrocytic brain tumors in human adults. The tumor suppressor gene TP53 is commonly mutated and/or lost alterations often found combination with excessive growth factor signaling via PDGF/PDGFRα. Here, we have generated transgenic mice over‐expressing PDGFB brain, under control of GFAP promoter. These showed no phenotype, but on a Trp53 null background majority them developed tumors. This occurred at 2–6 months age displayed...
Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors (PDGFRs) are known to play important roles during development of the lungs, central nervous system (CNS), skeleton in several diseases. PDGF-C is a ligand for receptor PDGFRα. Mutations gene encoding have been linked clefts lip and/or palate humans, ablation 129/Sv background mice results death perinatal period. In this study, we report that C57BL/6 milder phenotype than mice, present phenotypic characterization...
Abstract Activation of the platelet‐derived growth factor receptor‐ α ( PDGFR ) signaling pathway is critically important during lung alveogenesis, process in development which alveoli are formed from terminal alveolar sacs. Several studies have aimed to characterize expression patterns and its two ligands PDGF ‐A ‐C) lung, but published analyses been limited embryonic and/or perinatal time points, no attempts made both receptor ligand simultaneously. In this study, we present a detailed map...
ABSTRACT Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFRα. Analysis Pdgfc null mice has demonstrated roles PDGF-C in palate closure and formation cerebral ventricles, but redundancy with other PDGFRα might obscure additional functions. In search further developmental PDGF-C, we generated that were double mutants Pdgfc−/− PdgfraGFP/+. These display a range severe phenotypes including spina bifida, lung emphysema, abnormal meninges...
Expression of the platelet-derived growth factor A-chain gene (Pdgfa) occurs widely in developing mouse, where it is mainly localized to various epithelial and neuronal structures. Until now, situ mRNA hybridization (ISH) has been only reliable method identify Pdgfa expression tissue sections or whole mount preparations. Validated protocols for detection PDGF-A protein by immunohistochemistry lacking. In particular, this hampered understanding pattern adult tissues, ISH technically...
Deregulation of platelet-derived growth factor (PDGF) signaling is a hallmark malignant glioma. Two alternatively spliced PDGF-A mRNAs have been described, corresponding to long (L) and short (S) isoform PDGF-A. In contrast PDGF-A(S), the PDGF-A(L) has lysine arginine rich carboxy-terminal extension that acts as an extracellular matrix retention motif. However, exact role how it functionally differs from shorter not well understood.We overexpressed transgene under control glial fibrillary...