Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA238730 | ENA |
REPOSITORIES: ENA
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Project description:There is a growing recognition of cerebrovascular contribution to neurodegenerative diseases. Cerebral amyloid angiopathy (CAA), characterised by amyloid-beta (AM-NM-2) deposits in the walls of intracerebral and leptomeningeal arteries, is evident in a majority of AlzheimerM-bM-^@M-^Ys disease patients and aged people. Here, we leverage on human pluripotent stem cells to generate vascular smooth muscle cells (SMCs) from neural crest progenitors, recapitulating brain vasculature-specific attributes in AM-NM-2 metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural crest-derived SMCs to mediate AM-NM-2 uptake and intracellular proteasomal degradation. Hypoxia significantly compromises the ability of SMCs in AM-NM-2 clearance by suppressing LRP1 expression. This enables us to develop an assay of AM-NM-2 uptake using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high throughput format, demonstrating the value of stem cell-based phenotypic screening for novel CAA therapeutics and drug repurposing. We adopted our previous SMC differentiation protocol (Cheung et al., 2012) to differentiate this intermediate neural crest population using platelet-derived growth factor BB (PDGF-BB, 10 ng/ml) and transforming growth factor-beta 1 (TGF-M-NM-21, 2ng/ml) for another 12 days. The resultant neural crest-derived SMCs (NCSMC) were then characterised in comparison to neuroectoderm-derived SMCs (NESMC) (Cheung et al., 2012) and positive control, human brain vascular SMCs (BVSMC).
2015-01-21 | E-GEOD-55173 | biostudies-arrayexpress
Project description:There is a growing recognition of cerebrovascular contribution to neurodegenerative diseases. Cerebral amyloid angiopathy (CAA), characterised by amyloid-beta (Aβ) deposits in the walls of intracerebral and leptomeningeal arteries, is evident in a majority of Alzheimer’s disease patients and aged people. Here, we leverage on human pluripotent stem cells to generate vascular smooth muscle cells (SMCs) from neural crest progenitors, recapitulating brain vasculature-specific attributes in Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural crest-derived SMCs to mediate Aβ uptake and intracellular proteasomal degradation. Hypoxia significantly compromises the ability of SMCs in Aβ clearance by suppressing LRP1 expression. This enables us to develop an assay of Aβ uptake using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high throughput format, demonstrating the value of stem cell-based phenotypic screening for novel CAA therapeutics and drug repurposing.
2015-01-21 | GSE55173 | GEO
Project description:Sympathetic neurons of SCG (Superior Cervical Ganglia) send axonal projections either along the external carotid arteries to innervate the salivary glands, or along the internal carotid arteries to the lacrimal and pineal glands, the eye, blood vessels and skin of the head, and the mucosa of the oral and nasal cavities. Previous studies using Wnt1Cre and R26R have defined the neural crest and mesodermal origins of vascular smooth muscle in the heart outflow tract and great vessels, although not specifically of the segments that are relevant for the projections of the SCG neurons. The third pharyngeal arch arteries are lined by neural crest-derived smooth muscle, and consequently, their derivatives, including the entirety of the external carotid arteries and only the base of the internal carotid arteries, also have a neural crest origin. In contrast, the dorsal aortae are lined by smooth muscle that is mesodermal in origin, and as a result, the internal carotid arteries from just above their origination from the common carotid arteries have a mesoderm-derived smooth muscle layer. To address the possibility that guidance cues for SCG neurons are selectively expressed by the external carotid vs. the internal carotid arteries, we isolated these segments of the vasculature from mouse embryos at E13.5 and extracted RNA to screen microarrays for differentially expressed genes. Experiment Overall Design: Vascular segments were isolated from 22 embryos at E13.5, pooled and extracted RNA for microarray screen. Total RNA samples from the internal or the external carotid arteries were subjected for two-round amplification to synthesize cRNA to probe microarray. Neither experimental nor technical replicate was made for this experiment. Experiment Overall Design: Vascular segments were isolated from 22 embryos at E13.5, pooled and extracted RNA for microarray screen. Total RNA samples from the internal or the external carotid arteries were subjected for two-round amplification to synthesize cRNA to probe microarray. Neither experimental nor technical replicate was made for this experiment.
2008-06-11 | E-GEOD-10360 | biostudies-arrayexpress
Project description:Sympathetic neurons of SCG (Superior Cervical Ganglia) send axonal projections either along the external carotid arteries to innervate the salivary glands, or along the internal carotid arteries to the lacrimal and pineal glands, the eye, blood vessels and skin of the head, and the mucosa of the oral and nasal cavities. Previous studies using Wnt1Cre and R26R have defined the neural crest and mesodermal origins of vascular smooth muscle in the heart outflow tract and great vessels, although not specifically of the segments that are relevant for the projections of the SCG neurons. The third pharyngeal arch arteries are lined by neural crest-derived smooth muscle, and consequently, their derivatives, including the entirety of the external carotid arteries and only the base of the internal carotid arteries, also have a neural crest origin. In contrast, the dorsal aortae are lined by smooth muscle that is mesodermal in origin, and as a result, the internal carotid arteries from just above their origination from the common carotid arteries have a mesoderm-derived smooth muscle layer. To address the possibility that guidance cues for SCG neurons are selectively expressed by the external carotid vs. the internal carotid arteries, we isolated these segments of the vasculature from mouse embryos at E13.5 and extracted RNA to screen microarrays for differentially expressed genes. Keywords: differential expression in genes expressed in two different vascular segments.
2008-04-09 | GSE10360 | GEO
Project description:The epicardium, an epithelium covering the heart, is essential for cardiac development. During embryogenesis, the epicardium provides instructive signals for the growth and maturation of cardiomyocytes and for coronary angiogenesis. We generated an in vitro model of human embryonic epicardium derived from human pluripotent stem cells (hPSC-epi). These cells were able to differentiate into cardiac fibroblasts (cf) and smooth muscle cells (smc) in vitro (hPSC-epi-cf and hPSC-epi-smc respectively). Furthermore, we showed that they improved maturation of hPSC-derived cardiomyocytes (hPSC-cardio) in vitro while neural crest cells derived from hPSC (hPSC-NC) could not. Furthermore, they improved survival of hPSC-cardio and stimulated angiogenesis when injected in a rat model of myocardium infarction. We performed mRNA sequencing of the hPSC-epi, hPSC-epi-cf, hPSC-smc and hPSC-NC in order to identify the secreted molecules specifically produced by the hPSC-epi and/or its derivatives in comparison with the hPSC-NC. Vascular smooth muscle cells have different embryonic origins and different properties depending on their location in the body. The coronary smooth muscle cells come from the epicardium while the aortic ones come from the mesoderm or the neural crest. We performed mRNA sequencing of human coronary artery smc and human aortic smc to identify a specific signature of the coronary smc. We also compared the genes expressed in the hPSC-epi-smc and the smc derived from hPSC-derived lateral plate mesoderm.
2019-05-13 | GSE122714 | GEO
Project description:Transcriptome analysis of vascular smooth muscle cells differentiated from iPS-derived neural crest stem cells in Moyamoya disease Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by steno-occlusive changes in the cerebral arteries at the base of the brain with unknown etiology, although histopathological features have demonstrated as fibrocellular thickening of the intima and medial thinning on the steno-occlusive arteries. However, the pathophysiology of proliferating cells in the thickened intima is still obscure. Furthermore, biological features of the vascular smooth muscle cells are unclear in MMD. Here, we aimed to analyze whole genome gene expression profile in VSMC using induced pluripotent stem (iPS) cell line. We generated iPS cell line from the blood of MMD with RNF213 R4810K risk allele (rs112735431) or healthy control without the risk allele. VSMCs were differentiated from iPS-derived neural crest stem cells. As a result, we successfully established cranio-cervical region specific VSMC confirmed by immunocytochemistry. Biological cellular features, including cellular proliferation, migration, and contraction ability were similar in VSMCs between MMD and control. Genome-wide gene expression analysis showed similar transcriptome profile in the VSMCs between MMD and control. Differential gene expression analysis in MMD-VSMC revealed 6 differentially expressed genes (4 upregulated, 2 down regulated in MMD), including decorin (DCN, upregulated in MMD), playing an inhibitory role in angiogenesis. In conclusion, VSMCs are not impaired in cellular function with similar transcriptome profile in MMD compared to healthy control. Since many previous studies have shown impaired EC features in MMD, our study suggests EC may play more role in the vascular pathogenesis in MMD rather than VSMC.
2020-09-11 | GSE131293 | GEO
Project description:To better understand the role of lineage in smooth muscle cell heterogenity along the length of the aorta, we performed bulk RNA-sequencing transcriptomic analysis on secondary heart field (SHF)-derived and cardiac neural crest derived (CNC)-derived sorted cells from murine aortas.
2022-03-14 | GSE189544 | GEO
Project description:For in vitro disease modeling of LDS, we used healthy donor cells (TGFBR1+/+), and generated heterozygote (TGFBR1A230T/+), and homozygote (TGFBR1A230T/A230T) knock-in clones using CRISPR-Cas9 gene editing. We also generated hiPSC from peripheral blood mononuclear cells harvested from an LDS patient, and corrected the mutation in the patient-derived hiPSC. To address the lineage-specific effects of TGFBR1A230T, and SMAD3c.652delA/+, hiPSC were differentiated into cardiovascular progenitor cell-derived smooth muscle cells (CPC-SMC), and neural crest stem cell-derived smooth muscle cells (NCSC-SMC) using in vitro differentiation protocols. We performed large-scale single cell profiling of the resulting CPC-SMC and NCSC-SMC.
2021-08-04 | GSE175647 | GEO
Project description:During development, neural crest cells are induced by signaling events at the neural plate border of all vertebrate embryos. Initially arising within the central nervous system, NC cells subsequently undergo an epithelial to mesenchymal transition to migrate into the periphery, where they differentiate into diverse cell types. Here we provide evidence that postnatal human epidermal keratinocytes, in response to FGF2 and IGF1 signals, can be reprogrammed toward a neural crest fate. Genome-wide transcriptome analyses show that keratinocyte-derived NC cells are similar to those derived from human embryonic stem cells. Moreover, they give rise in vitro and in vivo to neural crest derivatives such as peripheral neurons, melanocytes, Schwann cells and mesenchymal cells (osteocytes, chondrocytes, adipocytes and smooth muscle). By demonstrating that human KRT14+ keratinocytes can form neural crest cells, even from clones of single cells, our results have important implications in stem cell biology and regenerative medicine.
2016-11-20 | GSE72268 | GEO
Project description:To model Hutchinson-Gilford Progeria syndrome (HGPS), we differentiated patient-derived induced pluripotent stem cells (iPSCs) to vascular smooth muscle cells (VSMCs). We then performed gene expression profiling analysis using data obtained from RNA-seq of the serially passaged cells at passage7 and passage 14.
2024-03-07 | GSE231761 | GEO