| 1. |
- Enarsson, Maria, et al.
(författare)
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Extracellular signal-regulated protein kinase signaling is uncoupled from initial differentiation of central nervous system stem cells to neurons
- 2002
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Ingår i: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 1:2, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about signaling pathways in response to external signals is needed to understand the regulation of stem cell proliferation and differentiation toward particular cell fates. The Ras/extracellular signal-regulated kinase (ERK) pathway has been suggested to play an essential role in neuronal differentiation. We have examined ERK signaling in the transition from multipotent stem cell to post-mitotic progeny using primary stem cells from the rat embryonic cortex. Fibroblast growth factor-2 (FGF-2) is a stem cell mitogen, whereas platelet-derived growth factor AA (PDGF-AA) expands a pool of committed neuronal precursors from stem cells. When comparing ERK activation by these growth factors, we found that FGF-2 stimulates high and PDGF-AA lower levels of ERK phosphorylation in stem cells. Differentiation was monitored as down-regulation of the bHLH transcription factor mammalian achaete-scute homologue-1 (MASH1). Even in the absence of active ERK, MASH1 became down-regulated and microtubule-associated protein 2-positive cells could form. Thus, ERK activation seems dispensable for the earliest steps of CNS stem cell differentiation.
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| 2. |
- Erlandsson, Anna, et al.
(författare)
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Immature neurons from CNS stem cells proliferate in response toplatelet-derived growth factor
- 2001
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 21:10, s. 3483-3491
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Tidskriftsartikel (refereegranskat)abstract
- Identifying external signals involved in the regulation of neural stem cell proliferation and differentiation is fundamental to the understanding of CNS development. In this study we show that platelet-derived growth factor (PDGF) can act as a mitogen for neural precursor cells. Multipotent stem cells from developing CNS can be maintained in a proliferative state under serum-free conditions in the presence of fibroblast growth factor-2 (FGF2) and induced to differentiate into neurons, astrocytes, and oligodendrocytes on withdrawal of the mitogen. PDGF has been suggested to play a role during the differentiation into neurons. We have investigated the effect of PDGF on cultured stem cells from embryonic rat cortex. The PDGF alpha-receptor is constantly expressed during differentiation of neural stem cells but is phosphorylated only after PDGF-AA treatment. In contrast, the PDGF beta-receptor is hardly detectable in uncommitted cells, but its expression increases during differentiation. We show that PDGF stimulation leads to c-fos induction, 5'-bromo-2'deoxyuridine incorporation, and an increase in the number of immature cells stained with antibodies to neuronal markers. Our findings suggest that PDGF acts as a mitogen in the early phase of stem cell differentiation to expand the pool of immature neurons.
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| 3. |
- Erlandsson, Anna, 1973-
(författare)
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Neural Stem Cell Differentiation and Migration
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neural stem cells are the precursors of neurons, astrocytes and oligodendrocytes. During neural development, the division of stem cells takes place close to the lumen of the neural tube, after which they migrate to their final positions within the central nervous system (CNS). Soluble factors, including growth factors, regulate neural stem cell proliferation, survival, migration and differentiation towards specific cell lineages.This thesis describes the function of platelet-derived growth factor (PDGF) and stem cell factor (SCF) in neural stem cell regulation. PDGF was previously suggested to stimulate neuronal differentiation, but the mechanisms were not defined. This study shows that PDGF is a mitogen and a survival factor that expands a pool of immature cells from neural stem cells. The PDGF-treated cells can be stained by neuronal markers, but need further stimuli to continue their maturation. They can become either neurons or glia depending on the secondary instructive cues. Moreover, neural stem cells produce PDGF. Inhibition of this endogenous PDGF negatively affects the cell number in stem cell cultures. We find that SCF stimulates migration and supports the survival of neural stem cells, but that it has no effect on their proliferation or differentiation into neurons and glia. Intracellular signaling downstream from the receptors for PDGF and SCF includes activation of extracellular signal-regulated kinase (ERK). This investigation shows that active ERK is not needed for the differentiation of stem cells into neurons, at least not during early stages.Neural stem cells have a future potential in the treatment of CNS disorders. To be able to use neural stem cells clinically we need to understand how their proliferation, differentiation, survival and migration are controlled. The results presented in this thesis increase our knowledge of how neural stem cells are regulated by growth factors.
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| 4. |
- Erlandsson, Anna, et al.
(författare)
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Stem cell factor is a chemoattractant and a survival factor for CNS stem cells
- 2004
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 301:2, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- Migration of neural cells to their final positions is crucial for the correct formation of the central nervous system. Several extrinsic factors are known to be involved in the regulation of neural migration. We asked if stem cell factor (SCF), well known as a chemoattractant and survival factor in the hematopoietic lineage, could elicit similar responses in neural stem cells. For that purpose, a microchemotaxis assay was used to study the effect of SCF on migration of neural stem cells from the embryonic rat cortex. Our results show that SCF-induced chemotaxis and that specific antibodies to SCF or tyrosine kinase inhibitors abolished the migratory response. The SCF-receptor, Kit, was expressed in neural stem cells and in their differentiated progeny. We also show that SCF is a survival factor, but not a mitogen or a differentiation factor for neural stem cells. These data suggest a role for SCF in cell migration and survival in the developing cortex.
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| 5. |
- Erlandsson, Martin, et al.
(författare)
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SIRII SPINE documented and quality reviewed environmental data
- 2003
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- One of the most significant obstacles in working with LCA and other system analytical tools where enviromental data are used, is the availability of adequate and well-documented inventory (environmental) data. Furthermore, it is preferable if the quality data has been reviewed to some degree. Both process knowledge and environmental competence are needed in order to review environmental data. The Sirii Environmental Data Network holds this unique competence profile, which enables the network to review environmental data with respect to the correctness of documentation as well as the reasonableness of the numerical value. The routine for review of Sirii SPINE documented data is presented in this report.
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| 6. |
- Erlandsson, Martin, et al.
(författare)
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Sirii SPINE dokumenterade och kvalitetssäkrade miljödata
- 2002
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det är allmänt känt att en av de viktigaste begränsningarna i arbetet med LCA och andra systemanalytiska verktyg som använder numeriska miljödata, är tillgången på väldokumenterade inventeringsdata. Det är vidare önskvärt att data är kvalitetssäkrade i någon bemärkelse. För att kunna kvalitetssäkra miljödata krävs både processkunnande och miljökompetens. Denna unika kompetensprofil besitter Sirii Miljödata Nätverk. En sådan kompetensprofil gör det möjligt att inte bara kvalitetssäkra miljödata med avseende på dokumentationens riktighet, utan även med avseende på rimligheten i de numeriska värdena. Rutinen för denna kvalitetssäkring finns redovisad i denna rapport.
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| 7. |
- Forsberg-Nilsson, Karin, et al.
(författare)
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Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF-B in myelinating tracts
- 2003
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Ingår i: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 41:3, s. 276-89
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) influences the generation of neurons and glia during embryogenesis and in early postnatal life. In an attempt to determine the consequences of an overexpression of PDGF-B during the first weeks of life, we targeted transgenic expression of a human PDGF-B cDNA to myelinating tracts using the promoter region of the myelin basic protein (MBP) gene. Transgenic mRNA and protein were expressed in the brain and the expression profile of the human PDGF-B during early postnatal development closely paralleled that of the endogenous mouse MBP gene. The gross morphological appearance of transgenic brains was normal but at the cellular level several phenotypic alterations could be identified. In white matter tracts such as the corpus callosum and cerebellar medulla, there was a marked hypercellularity. The number of oligodendrocyte precursors was increased and astrocytes were more abundant. In adult mice carrying the MBP-PDGF-B transgene, however, myelination appeared normal and the amount of oligodendrocytes was similar to that of control littermates. In addition to the phenotypic alterations in the brain, investigation of eye structure revealed a striking disorganization of retinal architecture. The retina was folded with cells collected in papillar or follicular-like structures. Retinal whole mount preparations after India ink perfusion revealed capillary disorganization with large-caliber vessels supporting only a few fine branches. Our observations strengthen the notion that PDGF is an important effector molecule in postnatal CNS development.
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| 8. |
- Hagbeg, Bengt, et al.
(författare)
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Odd MECP2-mutated Rett variant : long-term follow-up profile to age 25
- 2003
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Ingår i: European journal of paediatric neurology. - : Elsevier BV. - 1090-3798 .- 1532-2130. ; 7:6, s. 417-421
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Tidskriftsartikel (refereegranskat)abstract
- A 25-year-old MECP2-mutated female with odd developmental and dyspraxic/ataxic features, followed up through two decades, is reported. She does not fit either the classical Rett syndrome or the criteria required for any Rett variant phenotypes so far described. Nevertheless, she belongs clinically to the latter group. This case deserves attention in order, among other things, to provide important clues to better understand the puzzling battery of neuroimpairments and behavioural abnormalities met in classical Rett phenotypes and Rett variants defined thus far.
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