Pericytes and perivascular fibroblasts contribute to central nervous system fibrosis in a region dependent manner(DH SmartSeq)
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PROVIDER: PRJNA1106449 | ENA |
REPOSITORIES: ENA
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Project description:Fibrotic scar tissue formation is conserved throughout the central nervous system in humans and mice, and impairs tissue regeneration and functional recovery. However, the origin of scar-forming stromal fibroblasts is controversial. Here, we show that stromal fibroblasts found after spinal cord injury derive from two populations of perivascular cells that are anatomically and transcriptionally defined as pericytes and perivascular fibroblasts. We identify two distinct perivascular cell populations, which activate and transcriptionally converge on the generation of stromal myofibroblasts after injury. Our results suggest potential targets to improve tissue regeneration and functional recovery after central nervous system injuries.
2024-05-10 | GSE266250 | GEO
Project description:Fibrotic scar tissue formation is conserved throughout the central nervous system in humans and mice, and impairs tissue regeneration and functional recovery. However, the origin of scar-forming stromal fibroblasts is controversial. Here, we show that stromal fibroblasts found after spinal cord injury derive from two populations of perivascular cells that are anatomically and transcriptionally defined as pericytes and perivascular fibroblasts. We identify two distinct perivascular cell populations, which activate and transcriptionally converge on the generation of stromal myofibroblasts after injury. Our results suggest potential targets to improve tissue regeneration and functional recovery after central nervous system injuries.
2024-05-10 | GSE266251 | GEO
Project description:Fibrotic scar tissue formation is conserved throughout the central nervous system in humans and mice, and impairs tissue regeneration and functional recovery. However, the origin of scar-forming stromal fibroblasts is controversial. Here, we show that stromal fibroblasts found after spinal cord injury derive from two populations of perivascular cells that are anatomically and transcriptionally defined as pericytes and perivascular fibroblasts. We identify two distinct perivascular cell populations, which activate and transcriptionally converge on the generation of stromal myofibroblasts after injury. Our results suggest potential targets to improve tissue regeneration and functional recovery after central nervous system injuries.
2024-05-10 | GSE229916 | GEO
Project description:Pericytes and perivascular fibroblasts contribute to central nervous system fibrosis in a region dependent manner (DH express)
| PRJNA1106448 | ENA
Project description:Pericytes and perivascular fibroblasts contribute to central nervous system fibrosis in a region dependent manner
| PRJNA956577 | ENA
Project description:Brain perivascular cells have been recently identified as new mesodermal cell type of the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and â to a lesser extend â tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely discussed for the use in cell therapy in many neurological disorders. Therefore it is of importance to better understand the âintrinsicâ MSC population of the human brain. Here we systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells to fetal and adult human brain-derived NSCs and adult human bone marrow derived MSCs. We found that adult human brain pericytes can be isolated from hippocampal as well as cortical white matter, are â in contrast to adult human NSCs â easily expandable in monolayer cultures and show high similarities to human bone marrow-derived MSCs both regarding surface marker expression and whole transcriptome analysis. Human brain pericytes differentiated only in negligible amounts into neuroectodermal cell types using various differentiation conditions but efficiently differentiated into mesodermal progenies. Thus bone marrow-derived MSCs resemble human brain pericytes and might be therefore very interesting for possible autologous NPC-based treatment strategies, cell therapeutic approaches of neurological diseases. For the gene expression microarray analysis we used the Affymetrix U133A chips The whole procedure was performed following the manufacturer's standard protocol (Affymetrix, Santa Clara, CA). For the data processing, normalization was calculated with the GCRMA (GC content corrected Robust Multi-array Analysis) algorithm. Data post-processing and graphics was performed with in-house developed functions in Matlab. 17 samples were analyzed fNSC, Neural Stem Cell, 2 replicates ANPC-hip, adult Neuroprogenitor - Cell Hippocampus, 3 replicates ANPC-wm, adult Neuroprogenitor Cell - White Matter, 3 replicates ABPMC-hip, adult Brain Perivascular Mesodermal Cell - Hippocampus, 3 replicates ABPMC-wm, adult Brain Perivascular Mesodermal Cell - White Matter, 3 replicates MSC, Mesenchymal Stem Cell, 3 replicates
2015-11-03 | E-GEOD-62505 | biostudies-arrayexpress
Project description:Diabetic retinopathy (DR) is the leading cause of blindness in working-age people. Pericyte loss is one of the pathologic cellular events in DR, which weakens the retinal microvessels. Damages to the microvascular networks are irreversible and permanent, thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human ESCs (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin (STZ)-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells using a natural selection method without cell sorting processes. As a cellular model of pericytes, hESC-PVPCs exhibited marker expressions such as CD140B, CD146, NG2, and functional characteristics of pericytes. Following a single intravitreal injection into diabetic Brown Norway (BN) rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature, and stabilized blood-retinal barrier (BRB) breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization.
2016-01-22 | GSE77114 | GEO
Project description:The interplay of cerebromicrovascular endothelial cells, pericytes and perivascular macrophages is central to the recruitment of neutrophils across the blood-brain barrier into the brain, and therefore to the CNS inflammatory response. This experiment examined the endothelial response to direct stimulation in the presence or absence of pericytes to explore the effect of co-culture on the endothelial inflammatory response. It also assessed the endothelial response to signalling by monocyte-derived macrophages, modelling perivascular macrophages, the only canonical innate immune cell found within the perivascular space.
2022-08-31 | E-MTAB-11129 | biostudies-arrayexpress
Project description:The role of perivascular cell heterogeneity in tumor metastasis remains unknown. Here, we dissected the heterogeneity of perivascular cells by single-cell RNA sequencing and defined 13 subpopulations of pericytes within human colorectal cancers (CRC). Among them, an extracellular matrix (ECM)-rich subpopulation of TCF21high tumor pericytes (TPCs) was identified, which highly correlated with metastatic potentials in human CRC patients. Pericyte-specific conditional deletion of Tcf21 in mice mitigated CRC metastasis by decreasing perivascular ECM resmodeling, maintaining the integrity of the basement membrane, and reducing circulating cancer cells. Conversely, co-injection of CRC cells with TCF21high TPCs markedly promoted metastasis. Mechanistically, high expression of TCF21 in TPCs altered ECM stiffness, collagen deposition/rearrangement, and basement membrane degradation, which collectively instigated tumor cell intravasation and metastasis. Compelling experimental evidence showed that the loss of integrin α5 activated the FAK/PI3K/AKT axis, impaired DNA hypermethylation of TCF21, leading to high expression of TCF21 in TPCs. Our data provide new mechanistic insights into functions of a specific subpopulation of perivascular cells in promoting cancer metastasis and therapeutic targeting of metastasis-promoting TPCs may provide a new paradigm for cancer therapy.
2023-03-01 | GSE199726 | GEO
Project description:Pericytes/vascular smooth muscle cells (VSMCs), regulated by platelet-derived growth factor receptor β (PDGFRβ) signaling, play important roles in endothelial survival and vascular stability. Here we report that treatment with imatinib, an inhibitor of PDGFRβ, led to significant tumor growth impairment associated with increased apoptosis in human lymphoma xenografts including Farage, Karpas422 and OCI-Ly7 in SCID mice. Confocal analysis of the tumor tissue showed decreased microvessel density, decreased vascular flow, and increased vascular leak in the imatinib-treated cohorts. Imatinib targeted tumor-associated PDGFRβ+ pericytes in vivo by inducing apoptosis and disruption of the PDGFRβ+ perivascular network, and PDGFRβ+ VSMC in vitro by inhibition of proliferation. FACS analysis of mononuclear cell suspension of tumor tissues revealed decreased mature pericytes and endothelial cells, as well as their progenitors with imatinib treatment. Compared to imatinib, treatment with anti-PDGFRβ monoclonal antibody partially inhibited the growth of Farage lymphomas. Lastly, microarray analysis of differentially expressed genes in PDGFRβ+ VSMC following imatinib treatment showed significant down-regulation of genes implicated in proliferation, survival and angiogenesis, including those within PI3K/AKT and MAPK/ERK1/2 pathways downstream of PDGFRβ signaling. Taken together, targeting PDGFRβ+ pericytes in lymphoma presents a novel and complementary target to endothelial cells for efficacious antiangiogenic therapy. PDGFRb+ murine vascular smooth muscle cells (VSMCs) were treated in 10 uM imatinib for 24 or 48 hours. Gene expression changes in response to imatinib treatment were examined using NimbleGen MM8_60mer gene expression microarrays by comparing expression patterns at 24- and 48-hours treatment to the baseline level (0 hours).
2013-04-22 | E-GEOD-30752 | biostudies-arrayexpress