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2. |
- Anderson, Emma S., 1975-, et al.
(author)
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Molecular heterogeneity of oligodendrocytes in chicken white matter
- 1999
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In: Glia. - 0894-1491 .- 1098-1136. ; 27:1, s. 15-21
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Journal article (peer-reviewed)abstract
- The classical studies by Del Rio Hortega (Mem. Real. Soc. Espan. Hist. Nat. 14:40–122, 1928) suggest that the oligodendrocyte population includes four morphological subtypes. Recent data from the cat and the rat show that the anatomy of oligodendrocytes related to early myelinating prospective large fibers differs from that of oligodendrocytes related to late myelinating prospective small fibers. After application of a polyclonal antiserum to cryostat sections from the chicken CNS, we noted that glial cells in the spinal cord white matter had become labeled. Analysis of the occurrence and cellular localization of this immunoreactivity—the T4-O immunoreactivity—in the CNS of the adult chicken showed that T4-O immunoreactive cells are enriched in the ventral funiculus and superficially in the lateral funiculus of the spinal cord, where they are co-localized with large fibers. Double staining with T4-O antiserum and anti-GFAP or the lectin BSI-B4 revealed that T4-O immunoreactive cells are not astrocytes or microglia. Staining with anti-HSP108, a general marker for avian oligodendrocytes, showed that T4-O immunoreactivity defines an oligodendroglial subpopulation. A search for T4-O immunoreactivity in spinal cord white matter of some other vertebrates revealed that T4-O immunoreactive cells are not present in sections from fish, frog, turtle, rat, and rabbit spinal cord white matter. These results suggest the presence of a fiber size-related molecular heterogeneity among chicken white matter oligodendrocytes.
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3. |
- Liu, Li, et al.
(author)
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Glial Cell Responses, Complement and Clusterin in the Central Nervous System Following Dorsal Root Transection
- 1998
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In: Glia. - 0894-1491 .- 1098-1136. ; 23:3, s. 221-238
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Journal article (peer-reviewed)abstract
- We have examined the glial cell response, the possible expression of compounds associated with the complement cascade, including the putative complement inhibitor clusterin, and their cellular association during Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activity after rhizotomy, an exclusive involvement of microglia in this proliferation after peripheral nerve injury, but, in addition, a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after rhizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus. This is in marked contrast to the situation after peripheral nerve injury, which appears to activate the entire complement cascade in the vicinity of the central sensory processes. Clusterin, a multifunctional protein with complement inhibitory effects, was markedly upregulated in the dorsal funiculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocytes, possibly reflecting a degeneration process in these cells. The findings suggest that 1) complement expression by microglial cells is intimately associated with IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expression following neuronal injury but participates in regulating the state of oligodendrocytes during Wallerian degeneration.
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- Aldskogius, Håkan, et al.
(author)
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Microglia and Neuropathic Pain
- 2013
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In: CNS & Neurological Disorders. - : Wiley. - 1871-5273 .- 1996-3181. ; 12:6, s. 768-772
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Journal article (peer-reviewed)abstract
- Neuropathic pain is a serious consequence of injury or disease in the nervous system itself. Current treatment options for this condition are often unsatisfactory. From being originally viewed as a diseased caused by neuronal dysfunction, a growing body of evidence implicate activated microglia as a key player in the development of this pain condition. In this review, some of the evidence for this proposal is briefly discussed and placed in a translational context, pointing out the difficulties in translating commonly used animal models of neuropathic pain to the clinical condition, as well as emphasizing the broader role of activated microglia in the injured or diseased nervous system.
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7. |
- Alexander, Jes, et al.
(author)
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Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma
- 2020
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In: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:12, s. 2486-2502
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Journal article (peer-reviewed)abstract
- Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.
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9. |
- Blixt Wojciechowski, Anita, et al.
(author)
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Migratory capacity of the cell line RN33B and the host glial cell response after subretinal transplantation to normal adult rats
- 2004
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In: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 47:1, s. 58-67
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Journal article (peer-reviewed)abstract
- As previously reported, the brain-derived precursor cell line RN33B has a great capacity to migrate when transplanted to adult brain or retina. This cell line is immortalized with the SV40 large T-antigen and carries the reporter gene LacZ and the green fluorescent protein GFP. In the present study, the precursor cells were transplanted to the subretinal space of adult rats and investigated early after grafting. The purpose was to demonstrate the migration of the grafted cells from the subretinal space into the retina and the glial cell response of the host retina. Detachment caused by the transplantation method was persistent up to 4 days after transplantation, and then reattachment occurred. The grafted cells were shown to migrate in between the photoreceptor cells before entering into the plexiform layers. Molecules involved in migration of immature neuronal cells as the polysialylated neural cell adhesion molecule (PSA-NCAM) and the collapsing response-mediated protein 4 (TUC-4) was found in the plexiform layers of the host retina, but not in the grafted cells. The expression of the intermediate filaments GFAP, vimentin, and nestin was intensely upregulated immediately after transplantation. A less pronounced upregulation was observed on sham-operated animals. In summary, the RN33B cell line migrated promptly posttransplantation and settled preferably into the plexiform layers of the retina, the same layers where the migration cues PSA-NCAM and TUC-4 were established. In addition, both the transplantation method per se and the implanted cells caused an intense glial cell response by the host retina.
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12. |
- Caddick, Jenny, et al.
(author)
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Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage.
- 2006
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In: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 54:8, s. 840-849
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Journal article (peer-reviewed)abstract
- We have investigated the phenotypic and bioassay characteristics of bone marrow mesenchymal stromal cells (MSCs) differentiated along a Schwann cell lineage using glial growth factor. Expression of the Schwann cell markers S100, P75, and GFAP was determined by immunocytochemical staining and Western blotting. The levels of the stem cell markers Stro-1 and alkaline phosphatase and the neural progenitor marker nestin were also examined throughout the differentiation process. The phenotypic properties of cells differentiated at different passages were also compared. In addition to a phenotypic characterization, the functional ability of differentiated MSCs has been investigated employing a co-culture bioassay with dissociated primary sensory neurons. Following differentiation, MSCs underwent morphological changes similar to those of cultured Schwann cells and stained positively for all three Schwann cell markers. Quantitative Western blot analysis showed that the levels of S100 and P75 protein were significantly elevated upon differentiation. Differentiated MSCs were also found to enhance neurite outgrowth in co-culture with sensory neurons to a level equivalent or superior to that produced by Schwann cells. These findings support the assertion that MSCs can be differentiated into cells that are Schwann cell-like in terms of both phenotype and function.
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- Correa, Fernando, et al.
(author)
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The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK.
- 2011
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In: Glia. - : Wiley. - 1098-1136 .- 0894-1491. ; 59:5, s. 785-99
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Journal article (peer-reviewed)abstract
- The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0) ), used as control condition, or activated with different concentrations (0.1-1,000 ng mL(-1) ) of lipopolysaccharide (LPS) to produce MCM(0.1-1,000) . Acute exposure (24 h) to MCM(100) increased GSH, γGCL activity, the protein levels of γGCL-M, Nrf2, and activated JNK and ERK1/2 in astrocyte-rich cultures. In contrast, treatment with MCM(10) for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM(10) and MCM(100) . This down-regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM(10) on the inducible anti-oxidant defense in astrocyte-rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2.
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18. |
- Danilov, Alexandre, et al.
(author)
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Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone.
- 2009
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In: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; Aug 15, s. 136-152
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Journal article (peer-reviewed)abstract
- Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate olfactory bulb interneurons in the adult rodent brain. Based on their ultrastructural and antigenic properties, NSCs, transient amplifying precursor cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ ultrastructurally and at the light microscopy level, and to determine the antigenic properties of each cell type using gold and fluorescence immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal cells, displaced ependymal cells, and mature astrocytes. In contrast, transient amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts had epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFRalpha) expressed on the ciliary apparatus and were the only cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR and PDGFRalpha were associated with the microtubule of the mitotic spindle. Ependymal and displaced ependymal cells also expressed EGFR and PDGFRalpha on their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs disassemble the primary cilium and symmetrically distribute EGFR and PDGFRalpha among their progeny. (c) 2008 Wiley-Liss, Inc.
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21. |
- Forsberg-Nilsson, Karin, et al.
(author)
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Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF-B in myelinating tracts
- 2003
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In: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 41:3, s. 276-89
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Journal article (peer-reviewed)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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23. |
- Ghosh, Fredrik, et al.
(author)
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Müller cells in allogeneic adult rabbit retinal transplants.
- 2002
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In: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 40:1, s. 78-84
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Journal article (peer-reviewed)abstract
- Müller cell morphology and degree of activation in adult retinal transplants have, to our knowledge, never been reported previously. We transplanted adult rabbit neuroretinal full-thickness sheets, prepared under strict control, to the subretinal space of adult rabbits. After surviving 6-174 days, eyes were examined in the light microscope, and grafts displaying the normal laminated morphology were labeled with antibodies against vimentin and glial fibrillary acidic protein (GFAP). Müller cells in the grafts displayed the normal vertical arrangement, from outer limiting membrane to vitread endfeet. They showed an initial degree of activation, evident by GFAP upregulation, which diminished with increasing survival times, and was absent in the oldest specimens. In the host retina, Müller cells in the transplant area became progressively more disorganized with increasing survival times, and their degree of activation increased. Our results suggests that adult full-thickness neuroretinal grafts are structurally stable, even in long-term specimens, and thrive in spite of their allogeneic environment. The gliotic change seen in the host retina covering the graft is identical to the one seen in earlier reported eyes receiving embryonic grafts, and is due to the merangiotic nature of the rabbit neuroretina. GLIA 40:78-84, 2002. Copyright 2002 Wiley-Liss, Inc.
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24. |
- Ghosh, Fredrik
(author)
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Müller cells in long-term full-thickness retinal transplants.
- 2002
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In: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 37:1, s. 76-82
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Journal article (peer-reviewed)abstract
- Müller cells are essential in creating and maintaining intricate neuroretinal architecture. The functions of this important glial cell are not limited to mere support of the retinal neurons, but also include interaction in synaptic transmission and activation in response to retinal insult. In this study, we have examined Müller cell morphology and degree of activation in embryonic full-thickness rabbit neuroretinal grafts, which were positioned under the host retina using vitrectomy technique. After surviving 3-10 months, retinal specimens were examined with hematoxylin and eosin staining and immunohistochemical analysis of vimentin and glial fibrillary acidic protein (GFAP) expression. In the host retina covering the graft, outer layers were degenerated, and vimentin-labeled Müller cells in this area appeared short, disorganized, and displayed strong GFAP labeling. In the graft, vimentin-labeled Müller cells spanning the retinal layers in the normal manner were found. Müller cells in 3-month grafts were well labeled by GFAP, whereas in older grafts, GFAP labeling was very weak or absent. Our results suggest that Müller cells in well-laminated full-thickness retinal grafts display many of the normal morphological features and retain a normal organization even after prolonged survival times. The loss of the initial degree of Müller cell activation indicates a long-term stability of the graft. The degeneration and gliosis of the host retina covering the graft is best explained by the merangiotic nature of the rabbit retina and may limit the usefulness of the rabbit in retinal transplantation experiments.
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25. |
- Goncalves, Nadia P., et al.
(author)
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Schwann cell p75 neurotrophin receptor modulates small fiber degeneration in diabetic neuropathy
- 2020
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In: Glia. - : WILEY. - 0894-1491 .- 1098-1136. ; 68:12, s. 2725-2743
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Journal article (peer-reviewed)abstract
- Diabetic neuropathy has an incidence as high as 50% of diabetic patients and is characterized by damage to neurons, Schwann cells and blood vessels within the peripheral nervous system. The low-affinity neurotrophin receptor p75 (p75(NTR)), particularly expressed by the Schwann cells in the peripheral nerve, has previously been reported to play a role in developmental myelination and cell survival/death. Increased levels of p75(NTR), in the endoneurium and plasma from diabetic patients and rodent models of disease, have been observed, proposing that this receptor might be involved in the pathogenesis of diabetic neuropathy. Therefore, in this study, we addressed this hypothesis by utilizing a mouse model of selective nerve growth factor receptor (Ngfr) deletion in Schwann cells (SC-p75(NTR)-KO). Electron microscopy of sciatic nerves from mice with high fat diet induced obesity demonstrated how loss of Schwann cell-p75(NTR)aggravated axonal atrophy and loss of C-fibers. RNA sequencing disclosed several pre-clinical signaling alterations in the diabetic peripheral nerves, dependent on Schwann cell p75(NTR)signaling, specially related with lysosome, phagosome, and immune pathways. Morphological and biochemical analyses identified abundant lysosomes and autophagosomes in the C-fiber axoplasm of the diabetic SC-p75(NTR)-KO nerves, which together with increased Cathepsin B protein levels corroborates gene upregulation from the phagolysosomal pathways. Altogether, this study demonstrates that Schwann cell p75(NTR)deficiency amplifies diabetic neuropathy disease by triggering overactivation of immune-related pathways and increased lysosomal stress.
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27. |
- Gunnarson, Eli, et al.
(author)
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Identification of a molecular target for glutamate regulation of astrocyte water permeability
- 2008
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In: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 56:6, s. 587-596
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Journal article (peer-reviewed)abstract
- Astrocytes play a key role for maintenance of brain water homeostasis, but little is known about mechanisms of short-term regulation of astrocyte water permeability. Here, we report that glutamate increases astrocyte water permeability and that the molecular target for this effect is the aquaporin-4 (AQP4) serine 111 residue, which is in a strategic position for control of the water channel gating. The glutamate effect involves activation of group I metabotropic glutamate receptors (mGluR), intracellular calcium release, and activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and nitric oxide synthase (NOS). The physiological impact of our results is underlined by the finding that mGluR activation increases the rate of hypoosmotic tissue swelling in acute rat hippocampal slices. Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage. Thus, we have identified AQP4 as the molecular target for drugs that may attenuate the development of brain edema.
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35. |
- Hebsgaard, Josephine, et al.
(author)
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Dopamine neuron precursors within the developing human mesencephalon show radial glial characteristics.
- 2009
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In: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 57, s. 1648-1659
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Journal article (peer-reviewed)abstract
- Specification and differentiation of neural precursors into dopaminergic neurons within the ventral mesencephalon has been subject to much attention due to the implication of dopaminergic neurons in Parkinson's disease and the perspective of generating sources of therapeutically active cells to be used for cell replacement therapy for the disease. However, despite intensive research efforts, little is known about the characteristics of the dopamine neuron progenitors in human. We show that the dopamine neuron determinant LMX1a is expressed in the diencephalic and mesencephalic dopaminergic neuron domains during human development. Within the mesencephalon, LMX1a is expressed in the dopaminergic neurons and their progenitors located in the ventricular zone of the floor plate region. Furthermore, the neural progenitors in the developing human ventral mesencephalon have a radial morphology and express the radial glial markers Vimentin and BLBP. These radial glia are mitotic and act as precursors for the dopaminergic neurons. Finally, we show that progenitors isolated from the human ventral mesencephalon maintain their radial glial characteristics and neurogenic capacity after expansion in vitro, making them a promising future source of cells to be used in cell replacement therapy for Parkinson's disease. (c) 2009 Wiley-Liss, Inc.
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36. |
- Hede, Sanna-Maria, et al.
(author)
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GFAP promoter driven transgenic expression of PDGFB in the mouse brain leads to glioblastoma in a Trp53 null background
- 2009
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In: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 57:11, s. 1143-1153
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Journal article (peer-reviewed)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 in astrocytic brain tumors and the TP53 alterations are often found in combination with excessive growth factor signaling via PDGF/PDGFRalpha. Here, we have generated transgenic mice over-expressing human PDGFB in brain, under control of the human GFAP promoter. These mice showed no phenotype, but on a Trp53 null background a majority of them developed brain tumors. This occurred at 2-6 months of age and tumors displayed human glioblastoma-like features with integrated development of Pdgfralpha+ tumor cells and Pdgfrbeta+/Nestin+ vasculature. The transgene was expressed in subependymal astrocytic cells, in glia limitans, and in astrocytes throughout the brain substance, and subsequently, microscopic tumor lesions were initiated equally in all these areas. With tumor size, there was an increase in Nestin positivity and variability in lineage markers. These results indicate an unexpected plasticity of all astrocytic cells in the adult brain, not only of SVZ cells. The results also indicate a contribution of widely distributed Pdgfralpha+ precursor cells in the tumorigenic process.
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41. |
- Kaplan, Lew, et al.
(author)
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Retinal regions shape human and murine Müller cell proteome profile and functionality
- 2023
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In: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 71:2, s. 391-414
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Journal article (peer-reviewed)abstract
- The human macula is a highly specialized retinal region with pit-like morphology and rich in cones. How Müller cells, the principal glial cell type in the retina, are adapted to this environment is still poorly understood. We compared proteomic data from cone- and rod-rich retinae from human and mice and identified different expression profiles of cone- and rod-associated Müller cells that converged on pathways representing extracellular matrix and cell adhesion. In particular, epiplakin (EPPK1), which is thought to play a role in intermediate filament organization, was highly expressed in macular Müller cells. Furthermore, EPPK1 knockout in a human Müller cell-derived cell line led to a decrease in traction forces as well as to changes in cell size, shape, and filopodia characteristics. We here identified EPPK1 as a central molecular player in the region-specific architecture of the human retina, which likely enables specific functions under the immense mechanical loads in vivo.
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49. |
- Leiss, Lina, et al.
(author)
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Platelet-derived growth factor receptor α/glial fibrillary acidic protein expressing peritumoral astrocytes associate with shorter median overall survival in glioblastoma patients.
- 2020
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In: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:5, s. 979-988
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Journal article (peer-reviewed)abstract
- The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration of malignant cells. Astrocytes constitute a heterogeneous population of cells and have been linked to proliferation, migration, and drug sensitivity of glioblastoma (GBM) cells. Through double-immunohistochemical staining for platelet-derived growth factor receptor α (PDGFRα) and glial fibrillary acidic protein (GFAP), this study explored the intercase variability among 45 human GBM samples regarding density of GFAP+ peritumoral astrocytes and a subset of GFAP+ peritumoral astrocyte-like cells also expressing PDGFRα. Large intercase variability regarding the total peritumoral astrocyte density and the density of PDGFRα+/GFAP+ peritumoral astrocyte-like cells was detected. DNA fluorescence in situ hybridization analyses for commonly altered genetic tumor markers supported the interpretation that these cells represented a genetically unaffected host cell subset referred to as PDGFRα+/GFAP+ peritumoral astrocytes. The presence of PDGFRα+/GFAP+ peritumoral astrocytes was significantly positively correlated to older patient age and peritumoral astrocyte density, but not to other established prognostic factors. Notably, presence of PDGFRα+/GFAP+ peritumoral astrocytes, but not peritumoral astrocyte density, was associated with significantly shorter patient overall survival. The prognostic association of PDGFRα+/GFAP+ peritumoral astrocytes was confirmed in multivariable analyses. This exploratory study thus demonstrates previously unrecognized intercase variability and prognostic significance of peritumoral abundance of a novel PDGFRα+ subset of GFAP+ astrocytes. Findings suggest clinically relevant roles of the microenvironment of peritumoral GBM tissue and encourage further characterization of the novel astrocyte subset with regard to origin, function, and potential as biomarker and drug target.
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