Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro
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ABSTRACT:
PROVIDER: PRJNA504859 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8179895.fastq.gz | Fastqsanger.gz | |||
| SRR8179895_1.fastq.gz | Fastqsanger.gz | |||
| SRR8179895_2.fastq.gz | Fastqsanger.gz | |||
| SRR8179896.fastq.gz | Fastqsanger.gz | |||
| SRR8179896_1.fastq.gz | Fastqsanger.gz |
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Project description:Aims: Formation of a perfusable microvascular network (μVN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a μVN, but distinct stromal cell populations may play different roles in this process. Here we investigated the effects that two widely used stromal cells populations, fibroblasts (FBs) and pericytes (PCs), have on μVN formation. Methods and results: We examined the effects of adding defined stromal cell populations on the self-assembly of ECs derived from human endothelial colony forming cells (HECFCs) into perfusable μVNs in fibrin gels cast within a microfluidics chamber. ECs alone fail to fully assemble a perfusable μVN. Human lung FBs stimulate the formation of EC lined μVNs within microfluidic devices. RNA-seq analysis suggested that FBs produce high levels of hepatocyte growth factor (HGF), and addition of recombinant HGF improved μVN formation within devices. Human placental PCs could not substitute for FBs, but in the presence of FBs, PCs closely associated with ECs, formed a common basement membrane, extend microfilaments intercellularly, and reduced microvessel diameters. Conclusions: Different stromal cell types provide different functions in microvessel assembly by ECs. FBs support μVN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology.
2019-12-31 | GSE122389 | GEO
Project description:Formation of a perfusable microvascular network (?VN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a ?VN, but distinct stromal cell populations may play different roles in this process. Here we describe the differential effects that two widely used stromal cell populations, fibroblasts (FBs) and pericytes (PCs), have on ?VN formation. We examined the effects of adding defined stromal cell populations on the self-assembly of ECs derived from human endothelial colony forming cells (ECFCs) into perfusable ?VNs in fibrin gels cast within a microfluidic chamber. ECs alone failed to fully assemble a perfusable ?VN. Human lung FBs stimulated the formation of EC-lined ?VNs within microfluidic devices. RNA-seq analysis suggested that FBs produce high levels of hepatocyte growth factor (HGF). Addition of recombinant HGF improved while the c-MET inhibitor, Capmatinib (INCB28060), reduced ?VN formation within devices. Human placental PCs could not substitute for FBs, but in the presence of FBs, PCs closely associated with ECs, formed a common basement membrane, extended microfilaments intercellularly, and reduced microvessel diameters. Different stromal cell types provide different functions in microvessel assembly by ECs. FBs support ?VN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology.
| S-EPMC6944695 | biostudies-literature
Project description:The objective of the present study is to investigate the effect of a stroke mimic condition on human brain pericytes. Comparative gene expression analysis was performed using cultured human brain microvascular pericytes with 1% oxygen for 24 hours or with acidic condition at pH 6.5 for 24 hours. Gene expression was analyzed using 3D-Gene® Human 25k oligonucleotide microarrays and computational gene expression analysis tools. Incubation of cells under these conditions resulted in significant changes in numerous genes related with glycolysis, immune responses, and angiogenesis.
2019-02-01 | GSE109187 | GEO
Project description:The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming. Here, we show that abrupt destabilization of the higher-order chromatin topology that chaperones lineage memory of pericytes is driven by transient global transcriptional arrest. This leads within minutes to localized decompression of the repressed competing higher-order chromatin topology and expression of pro-neural genes. Transition to neural lineage is completed by probabilistic induction of R-loops in key myogenic loci upon re-initiation of RNA polymerase activity, leading to depletion of the myogenic transcriptome and emergence of the neurogenic transcriptome.
2021-11-04 | GSE187019 | GEO
Project description:The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming. Here, we show that abrupt destabilization of the higher-order chromatin topology that chaperones lineage memory of pericytes is driven by transient global transcriptional arrest. This leads within minutes to localized decompression of the repressed competing higher-order chromatin topology and expression of pro-neural genes. Transition to neural lineage is completed by probabilistic induction of R-loops in key myogenic loci upon re-initiation of RNA polymerase activity, leading to depletion of the myogenic transcriptome and emergence of the neurogenic transcriptome.
2021-11-04 | GSE187018 | GEO
Project description:The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming. Here, we show that abrupt destabilization of the higher-order chromatin topology that chaperones lineage memory of pericytes is driven by transient global transcriptional arrest. This leads within minutes to localized decompression of the repressed competing higher-order chromatin topology and expression of pro-neural genes. Transition to neural lineage is completed by probabilistic induction of R-loops in key myogenic loci upon re-initiation of RNA polymerase activity, leading to depletion of the myogenic transcriptome and emergence of the neurogenic transcriptome.
2021-11-04 | GSE187017 | GEO
Project description:The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming. Here, we show that abrupt destabilization of the higher-order chromatin topology that chaperones lineage memory of pericytes is driven by transient global transcriptional arrest. This leads within minutes to localized decompression of the repressed competing higher-order chromatin topology and expression of pro-neural genes. Transition to neural lineage is completed by probabilistic induction of R-loops in key myogenic loci upon re-initiation of RNA polymerase activity, leading to depletion of the myogenic transcriptome and emergence of the neurogenic transcriptome.
2021-11-04 | GSE187016 | GEO
Project description:Microvascular dysfunction has been proposed to drive heart failure with preserved ejection fraction (HFpEF), but the initiating molecular and cellular events are largely unknown. Our objective was to determine when microvascular alterations in HFpEF begin, how they contribute to disease progression, and how pericyte dysfunction plays a role herein. We aimed to assess microvascular dysfunction with respect to the development of cardiac dysfunction, in the Zucker fatty and spontaneously hypertensive (ZSF1) obese rat model of HFpEF at three time points: 6, 14, and 21 weeks of age. We found that pericyte loss was the earliest and strongest microvascular change, occurring before prominent echocardiographic signs of diastolic dysfunction were present. Pericytes were shown to be less proliferative and had a disrupted morphology at 14 weeks in the obese ZSF1 animals, who also exhibited an increased capillary luminal diameter and disrupted endothelial junctions. Pericytes exposed to oxidative stress in vitro showed downregulation of cell cycle associated pathways, and induced a pro-inflammatory state in endothelial cells upon co-culture. We propose pericytes are important for maintaining endothelial cell function, where loss of pericytes enhances the reactivity of endothelial cells to inflammatory signals and promotes microvascular dysfunction, thereby accelerating the development of HFpEF.
2023-12-29 | GSE251995 | GEO
Project description:Genomic and transcriptomic profiles of human brain microvascular pericytes upon neural transdifferentiation
| PRJNA777267 | ENA
Project description:Background: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, extracellular matrix (ECM) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel two-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue. This study investigated how ECM stiffness regulated microvascular ECs, pericytes, and their interactions. Methods: Primary microvessels were cultured in the TGM2D medium. Stiff ECM was prepared by incubating ECM solution in regular culture dishes for one hour followed by PBS wash. Soft ECM with Young’s modulus of approximately 6 kPa was used unless otherwise noted. Bone grafts were prepared from the rat skull. Immunostaining, RNA sequencing, qRT-PCR, western blotting, and knockdown experiments were performed on the cells. Results: Primary microvascular pericytes differentiated into myofibroblasts (NG2+αSMA+) on stiff ECM, even with the TGFβ signaling inhibitor A83-01. Soft ECM and A83-01 cooperatively maintained microvascular stability while inhibiting pericyte-myofibroblast differentiation (NG2+αSMA-/low). We thus defined two pericyte subpopulations: primary (NG2+αSMA-/low) and activated (NG2+αSMA+) pericytes. Soft ECM promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation in vivo. As Integrins are the major mechanosensor, we performed qRT-PCR screening of Integrin family members selected from RNA sequencing data. We found that Integrin β1 (Itgb1) was the major subunit downregulated by soft ECM and A83-01 treatment. Knocking down Itgb1 suppressed myofibroblast differentiation on stiff ECM. Interestingly, ITGB1 phosphorylation (Y783) was mainly located on microvascular ECs on stiff ECM, which promoted EC secretion of paracrine factors, including CTGF, to induce pericyte-myofibroblast differentiation. CTGF knockdown or monoclonal antibody treatment partially reduced myofibroblast differentiation, implying the participation of multiple pathways in fibrosis formation. Conclusions: Microvascular ECs mediate ECM stiffness-induced pericyte-myofibroblast differentiation through paracrine signaling.
2023-07-18 | GSE237069 | GEO