Smooth muscle cell reprogramming in aortic aneurysms [scRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE141031 | GEO | 2020/03/01
REPOSITORIES: GEO
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Project description:Smooth muscle cell TGFβ signaling is one of the primary drivers of smooth muscle cell maturation. Inhibition of smooth muscle cell TGFβ signaling in hyperlipidemic mice induces vessel wall inflammation and vessel wall dilation/dissection and leads aortic aneurysm. We performed bulk RNAseq method to examine smooth muscle cell gene expression profile using fresh human tissues from normal aortic media smooth muscle cells and aneurysm aortic media smooth muscle cells.
2020-03-01 | GSE140947 | GEO
Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.
2019-08-26 | GSE134557 | GEO
Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.
2019-08-26 | GSE134556 | GEO
Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.
2019-08-26 | GSE134555 | GEO
Project description:Ascending aortic aneurysms (AscAA) are a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Lineage tracing analysis showed that loss of Notch1 in the SHF reduces the number of SHF-derived smooth muscle cells in the aortic root, and RNA-seq analysis demonstrated distinct in vivo expression patterns between lineage-specific regions of the ascending aorta. Finally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 independently predisposes to AscAA. These findings are the first to demonstrate a SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.
2017-09-29 | GSE104365 | GEO
Project description:Persistent severe asthma is associated with hyper-contractile airways and structural changes in the airway wall, including an increased airway smooth muscle (ASM) mass. This study used gene expression profiles from asthmatic and healthy airway smooth muscle cells grown in culture to identify novel receptors and pathways that potentially contributed to asthma pathogenesis. We used microarrays to compare the gene expression between asthmatic and healthy airway smooth muscle cells to understand the underlying pathway contributing the differences in cellular phenotypes Asthmatic airway smooth muscle cells (ASMC) are intrinsically different and have a differential transcriptional response to pro-fibrotic, pro-proliferation and pro-inflammatory stimuli than ASMC from healthy patients. We sought to identify genes that are differentially expressed between asthmatic and healthy ASMC under various stimulations which mimic the asthmatic airways. To this end, we obtained human ASMC from bronchial biopsies and explanted lungs from doctor diagnosed asthmatic patients (n=3) and healthy controls (n=3). The ASMC were then grown in culture and treated with pro-fibrotic (Transforming growth factor beta (TGFβ)), pro-proliferation (Fetal Bovine Serum (FBS)) and pro-inflammatory stimuli (Interleukin-1 beta (IL-1β)) for 8 hours. Gene expression was then evaluated using Affymetrix Human Gene 1.0ST arrays.
2015-01-31 | E-GEOD-63383 | biostudies-arrayexpress
Project description:We used microarrays to characterize the global changes in gene expression within the ascending aorta of mice due to conditional disruption of TGF-M-NM-2 signaling in smooth muscle and/or due to heterozygous fibrillin-1 mutation. Myh11-CreERT2.Tgfbr2f/f (abbreviated as Cre.Tgfbr2) mice were cross-bred to Fbn1C1039G/+ (abbreviated as Fbn1C/+) mice and treated with vehicle or tamoxifen for 5 d starting at 4 wk of age to generate 4 groups of animals: 1) Cre.Tgfbr2-Veh: controls with intact TGF-M-NM-2 signaling and wild-type fibrillin-1 expression; 2) Cre.Tgfbr2-Tmx: conditional disruption of Tgfbr2 in smooth muscle with wild-type fibrillin-1 expression; 3) Fbn1C1039G.Cre.Tgfbr2-Veh: heterozygous expression of mutant fibrillin-1 with intact TGF-M-NM-2 signaling; and 4) Fbn1C1039G.Cre.Tgfbr2-Tmx: conditional disruption of Tgfbr2 in smooth muscle with heterozygous expression of mutant fibrillin-1. The animals were euthanized at 6 weeks of age and their ascending aortas (from above the coronary arteries to the first arch branch) were collected and total RNA was extracted.
2013-05-31 | E-GEOD-36778 | biostudies-arrayexpress
Project description:Pericytes (PCs) are microvascular mural cells which constituent the embryonic blood brain barrier (BBB) along with endothelial cells (ECs). During brain development, germinal matrix (GM) - a highly vascularized region rich in neuronal-glial precursors, is selectively vulnerable to hemorrhage in premature infants. The transforming growth factor β (TGFβ) pathway plays a crucial role in barrier development by regulating cellular cross talk between PCs and ECs. Indeed, murine embryos lacking TGFβ receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) and culminate in perinatal lethality. Mutant GM vessels display reduced PC and collagen coverage, abnormal vessel dilation and EC hyperproliferation. However, the mechanistic link between PC-specific deletion of ALK5 and aberrant EC behavior remains elusive. Herein, using bulk RNA sequencing from human brain PCs lacking ALK5 (siALK5) as well as murine vascular cells [PCs and ECs] isolated from embryonic brain at embryonic days E11.5 and E13.5 we establish that angiopoietin 2 (ANGPT2), a secreted angiogenic growth factor, is robustly repressed by the TGFβ pathway in PCs. Conversely, mutants lacking PC-ALK5 secrete higher levels of ANGPT2 resulting in overactivation of tyrosine protein kinase receptor (TIE2) and culminating in EC hyperproliferation, vessel dilation, BBB breakdown and GMH. PC-specific Angpt2 deletion or pharmacological inhibition in mutants improves GM vessel morphology, reduces EC proliferation and attenuates GMH pathogenesis. Taken together, we demonstrate that loss of TGFβ-mediated ANGPT2 repression in PCs is detrimental for BBB integrity and identify ANGPT2 as an important pathological target for GMH-IVH.
2024-06-30 | GSE269066 | GEO
Project description:Pericytes (PCs) are microvascular mural cells which constituent the embryonic blood brain barrier (BBB) along with endothelial cells (ECs). During brain development, germinal matrix (GM) - a highly vascularized region rich in neuronal-glial precursors, is selectively vulnerable to hemorrhage in premature infants. The transforming growth factor β (TGFβ) pathway plays a crucial role in barrier development by regulating cellular cross talk between PCs and ECs. Indeed, murine embryos lacking TGFβ receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) and culminate in perinatal lethality. Mutant GM vessels display reduced PC and collagen coverage, abnormal vessel dilation and EC hyperproliferation. However, the mechanistic link between PC-specific deletion of ALK5 and aberrant EC behavior remains elusive. Herein, using bulk RNA sequencing from human brain PCs lacking ALK5 (siALK5) as well as murine vascular cells [PCs and ECs] isolated from embryonic brain at embryonic days E11.5 and E13.5 we establish that angiopoietin 2 (ANGPT2), a secreted angiogenic growth factor, is robustly repressed by the TGFβ pathway in PCs. Conversely, mutants lacking PC-ALK5 secrete higher levels of ANGPT2 resulting in overactivation of tyrosine protein kinase receptor (TIE2) and culminating in EC hyperproliferation, vessel dilation, BBB breakdown and GMH. PC-specific Angpt2 deletion or pharmacological inhibition in mutants improves GM vessel morphology, reduces EC proliferation and attenuates GMH pathogenesis. Taken together, we demonstrate that loss of TGFβ-mediated ANGPT2 repression in PCs is detrimental for BBB integrity and identify ANGPT2 as an important pathological target for GMH-IVH.
2024-06-30 | GSE268575 | GEO
Project description:The goal of these studies was to delineate mechanisms of crosstalk between the atherosclerotic arterial wall of the aorta and the peripheral nervous system (PNS) in aged hyperlipidemic ApoE-deficient mice. We had observed by immunohistochemistry and morphometry that axon density of the PNS in adventitia segments that were located adjacent to advanced atherosclerotic plaques of aged hyperlipidemic ApoE-deficient mice were markedly higher than those adventitia segments that did not show adjacent atherosclerotic plaques in the intima layer. It is noteworthy in this connection that neither the media nor the intimal layer are innervated by axon endings. However, the adventitia layer of arteries is a conduit for axons and nerves of the PNS connecting the peripheral ganglia and peripheral organs including the spleen. In addition, we discovered (see references below) that atherosclerosis is sensed by the immune system of aged ApoE-deficient mice resulting in the formation of artery tertiary lymphoid organs in the adventitia layer of the arterial wall. To examine potential molecular mechanisms of the crosstalk between the disease aorta and the PNS, we isolated adventitia tissues and media tissues from aortas of ApoE-deficient mice and used wild-type mice as controls. Moreover, we observed that the sympathetic nervous system paraaortic and periaortic ganglia in aged ApoE-deficient but not of aged wild-type mice were infiltrated by leukocytes indicating that atherosclerosis is associated with major alterations of the PNS including axonogenesis and ganglionitis. To identify potential molecules involved in the crosstalk, we isolated respective tissues (media, adventitia, ganglia) by laser capture microdissection and generated large scale mRNA expression arrays to construct transcript maps that were assembled into transcript atlases. Publications related to this approach: Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors. Hu D, Mohanta SK, Yin C, Peng L, Ma Z, Srikakulapu P, Grassia G, MacRitchie N, Dever G, Gordon P, Burton FL, Ialenti A, Sabir SR, McInnes IB, Brewer JM, Garside P, Weber C, Lehmann T, Teupser D, Habenicht L, Beer M, Grabner R, Maffia P, Weih F, Habenicht AJ. Immunity. 2015 Jun 16;42(6):1100-15. doi: 10.1016/j.immuni.2015.05.015. Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis. Mohanta SK, Yin C, Peng L, Srikakulapu P, Bontha V, Hu D, Weih F, Weber C, Gerdes N, Habenicht AJ. Circ Res. 2014 May 23;114(11):1772-87. doi: 10.1161/CIRCRESAHA.114.301137. Review. Control of dichotomic innate and adaptive immune responses by artery tertiary lymphoid organs in atherosclerosis. Weih F, Gräbner R, Hu D, Beer M, Habenicht AJ. Front Physiol. 2012 Jul 6;3:226. doi: 10.3389/fphys.2012.00226. Laser-capture microdissection of hyperlipidemic/ApoE⁻/⁻ mouse aorta atherosclerosis. Beer M, Doepping S, Hildner M, Weber G, Grabner R, Hu D, Mohanta SK, Srikakulapu P, Weih F, Habenicht AJ. Methods Mol Biol. 2011;755:417-28. doi: 10.1007/978-1-61779-163-5_35. apoE-Adventitia arrays were submitted previously (GSM252007, GSM252008, GSM252009, GSM252010, GSM252011, GSM252014, GSM252015, GSM252016; GSE10000, GSE40156) and are now submitted together with new wild-type adventitia arrays not previously published in order to make all adventitia of ApoE-deficient mice and wild-type mice available in one new submission/location.
2022-02-27 | GSE94044 | GEO