Klf4 has an unexpected protective role in perivascular cells within the microvasculature
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA420953 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6342034.fastq.gz | Fastqsanger.gz | |||
| SRR6342035.fastq.gz | Fastqsanger.gz | |||
| SRR6342036.fastq.gz | Fastqsanger.gz | |||
| SRR6342037.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Recent smooth muscle cell (SMC) lineage tracing studies have demonstrated that SMCs undergo remarkable changes in phenotype during development of atherosclerosis, including loss of typical SMC markers such as ACTA2 and Klf4 dependent activation of multiple markers of macrophages and mesenchymal stem cells. Of major interest, we showed Klf4 in SMC is critical for overall lesion pathogenesis as SMC-specific conditional knockout (KO) of Klf4 resulted in smaller, more stable lesions that exhibited marked reductions in the numbers of SMC-derived macrophage-like and mesenchymal stem cell like cells. Herein we tested the hypothesis that Klf4 dependent SMC transitions are beneficial following myocardial infarction (MI). Utilizing SMC-specific lineage tracing mice +/- simultaneous SMC-specific conditional KO of Klf4, we demonstrate that SMCs express Klf4 and transition to a Klf4 dependent macrophage-like state as well as a Klf4 independent myofibroblast-like state. SMC specific, conditional KO of Klf4 resulted in marked exacerbation of heart failure following MI. Surprisingly, significant cardiac dilation was seen in SMC-Klf4 KO mice prior to MI. This cardiac dilation was accompanied by a reduction in peripheral resistance, as evidenced by a reduction in blood pressure, an increase in blood flow, and a larger passive diameter of mesenteric resistance arteries as measured by pressure myography. Klf4 ChIP-Seq analysis on the mesenteric resistance arteries identified potential Klf4 target genes in SMC at baseline in pathways including PDGF and FGF signaling previously shown to be important for perivascular cell investment. Interestingly, examination of microvascular tissue beds revealed gaps in lineage traced SMC coverage along the resistance arteries. Taken together, these results provide novel evidence that Klf4 has a critical maintenance role within microvascular SMCs, including being required for normal SMC coverage of resistance arteries as well as their function.
2020-12-01 | GSE107641 | GEO
Project description:Recent smooth muscle cell (SMC) lineage-tracing studies have revealed that SMCs undergo remarkable changes in phenotype during development of atherosclerosis. Of major interest, we demonstrated that Kruppel-like factor 4 (KLF4) in SMCs is detrimental for overall lesion pathogenesis, in that SMC-specific conditional knockout of the KLF4 gene ( Klf4) resulted in smaller, more-stable lesions that exhibited marked reductions in the numbers of SMC-derived macrophage- and mesenchymal stem cell-like cells. However, since the clinical consequences of atherosclerosis typically occur well after our reproductive years, we sought to identify beneficial KLF4-dependent SMC functions that were likely to be evolutionarily conserved. We tested the hypothesis that KLF4-dependent SMC transitions play an important role in the tissue injury-repair process. Using SMC-specific lineage-tracing mice positive and negative for simultaneous SMC-specific conditional knockout of Klf4, we demonstrate that SMCs in the remodeling heart after ischemia-reperfusion injury (IRI) express KLF4 and transition to a KLF4-dependent macrophage-like state and a KLF4-independent myofibroblast-like state. Moreover, heart failure after IRI was exacerbated in SMC Klf4 knockout mice. Surprisingly, we observed a significant cardiac dilation in SMC Klf4 knockout mice before IRI as well as a reduction in peripheral resistance. KLF4 chromatin immunoprecipitation-sequencing analysis on mesenteric vascular beds identified potential baseline SMC KLF4 target genes in numerous pathways, including PDGF and FGF. Moreover, microvascular tissue beds in SMC Klf4 knockout mice had gaps in lineage-traced SMC coverage along the resistance arteries and exhibited increased permeability. Together, these results provide novel evidence that Klf4 has a critical maintenance role within microvascular SMCs: it is required for normal SMC function and coverage of resistance arteries. NEW & NOTEWORTHY We report novel evidence that the Kruppel-like factor 4 gene ( Klf4) has a critical maintenance role within microvascular smooth muscle cells (SMCs). SMC-specific Klf4 knockout at baseline resulted in a loss of lineage-traced SMC coverage of resistance arteries, dilation of resistance arteries, increased blood flow, and cardiac dilation.
| S-EPMC6139624 | biostudies-literature
Project description:The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. We use a microvasculature-on-a-chip system as a PVN model to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs were found to preferentially localize in the perivascular zone, where they exhibited either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. The degree of co-localization between tumor cells and microvessels varied significantly across patients. To validate these results from the microvasculature-on-a-chip system, single-cell transcriptome sequencing (10 patients and 21,750 single cells in total) was performed to identify tumor cell subtypes. The co-localization coefficient was found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlated strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that our BTSC-on-a-chip model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions.
2019-02-15 | GSE125587 | GEO
Project description:Aim of this experiment was to characterize whether SPP1 released from the hippocampal perivascular space could imprint microglia transcriptional states. We performed scRNA-seq analysis on sorted CD140a+ perivascular fibroblast (PVF), CD45highCD11intCD206+ perivascular macrophage (PVM) and CD45intCD11intCX3CR1high microglial cell from dissected hippocampi of 6-month old wild type vs SPP1KO/KO vs AppNL-F mice vs AppNL-FxSpp1KO/KO mice. Cells were isolated from dissected hippocampi as previously described (Sala Frigerio et al.,2019).
2024-02-09 | E-MTAB-11918 | biostudies-arrayexpress
Project description:MEK5 is activated by shear stress in large vessel endothelial cells (ECs) and contributes to the suppression of pro-inflammatory changes in the arterial wall. We used microarray analyses of total RNA from MEK5/CA-transduced HDMECs compared to LacZ control-transduced HDMECs to identify distinct classes of several regulated genes, including KLF4, eNOS, and ICAM. We conclude that MEK5 activation by shear stress may modulate inflammatory responses in the microvasculature, and these actions are partly mediated by KLF4. Total RNA was isolated from 8 separate paired (derived from same primary isolate) MEK5/CA and LacZ transduced HDMEC lines
2010-12-31 | E-GEOD-25145 | biostudies-arrayexpress
Project description:MEK5 is activated by shear stress in large vessel endothelial cells (ECs) and contributes to the suppression of pro-inflammatory changes in the arterial wall. We used microarray analyses of total RNA from MEK5/CA-transduced HDMECs compared to LacZ control-transduced HDMECs to identify distinct classes of several regulated genes, including KLF4, eNOS, and ICAM. We conclude that MEK5 activation by shear stress may modulate inflammatory responses in the microvasculature, and these actions are partly mediated by KLF4.
2010-12-31 | GSE25145 | GEO
Project description:Retinal microvessels (RMVs) and brain microvessels (BMVs) were isolated from diabetic and nondiabetic rats. RNA were extracted, amplified and processed on Affymetrix rat 2.0 microarray Chips. Differently expressed genes (DEGs) between diabetic RMVs and nondiabetic RMVs, and between diabetic BMVs and nondiabetic BMVs were analyzed. Using these DEGs, we analyzed and compared the diabetic effects on the gene expression profiles in retinal microvasculature and brain microvasculature. In the brain microvasculature multiple compensatory mechanisms exists, serving to protect brain tissue from diabetic insults, whereas these mechanisms are not activated in the retinal microvasculature.
2020-03-31 | GSE113686 | GEO
Project description:Reveal the single-cell landscape of the stromal vascular fraction (SVF) of perivascular adipose tissue (PVAT) and show its tremendous heterogeneity and significant alterations in type 2 diabetes.
2024-08-27 | GSE275779 | GEO
Project description:Single-cell view and a novel protective macrophage subset in perivascular adipose tissue (PVAT) in T2DM
| PRJNA1152965 | ENA
Project description:Glioblastoma stem cells (GSCs) have been reported to be found near the blood vessels. We wanted to identify the perivascular GSCs by combining the label retention approach with vascular perfusion. GSCs, like most of the stem cells, are in a quiescent state. Label retention approach involves staining the cells with a uniform membrane labeling dye (PKH26) and allowing them to grow in vivo in NOD SCID mice. Slow-dividing stem cells will retain the dye to a greater extent and perivascular cells are identified by injecting the mice with vascular perfusion dye (Hoechst 33342) 5 min prior to sacrifice. Perivascular GSCs (positive for Hoechst 33342 and pKH26 dye - dubbed as H+P+) were compared with the rest of the perivascular glioma cells (H+P-).
2022-01-01 | E-MTAB-9607 | biostudies-arrayexpress