Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1153322 | 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:The LIM-only protein FHL2 is expressed in SMCs and inhibits SMC-rich lesion formation. However, the underlying mechanism behind FHL2's action in SMCs has been only partially resolved. To further elucidate the role of FHL2 in SMCs we compared the transcriptome of cultured SMCs derived from wild-type (WT) and FHL2-knockout (KO) mice. Comparison of gene expression in aortic smooth muscle cells (SMCs) isolated from WT and FHL2-knockout (FHL2-KO) mice. SMCs isolated from three mouse aortas were pooled (Kurakula et al, PLOS One, 2014). Both for WT and FHL-KO mice three batches of SMCs (derived from 9 mice) were cultured. The SMCs were grown to confluency and maintained in serum-free medium for 48 hrs before harvest. Subsequently, RNA was isolated for gene expression profiling.
2014-10-07 | E-GEOD-56860 | biostudies-arrayexpress
Project description:Purpose: global gene expression profiling of H1 and iPSC derived endothelial cells (ECs) and smooth mucle cells (SMCs). Methods: SMART-seq2 amplified polyA RNA from undifferentiated H1 cells and iPSCs (in biological duplicates), cardiovascular progenitor cells, endothelial cells (ECs) and smooth muscle cells (SMCs) Results: Insulin free condition promoted cardiovascular mesoderm, endothelial and smooth muscle differentiation. Conclusions: the gene expression profiles of ECs and SMCs differentiated in insulin free medium confirmed that they are true ECs and SMCs.
2021-05-20 | GSE114776 | GEO
Project description:Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca2+ entry and gene expression profiles compared with those from control-iPSCs. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in the iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed a statistically significant correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that the serum MMP1 levels may be a novel risk factor and become more beneficial when combined with other risk factors. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors. The gene expression profiles of vascular endothelia and smooth muscle cells derived from control- and ADPKD-iPSCs were analyzed. Seven control-iPSC derived endothelial cells (ECs), seven ADPKD-iPSC derived ECs, ten control-iPSC derived vascular smooth muscle cells (SMCs), and seven ADPKD-iPSC derived SMCs were analyzed.
2016-08-04 | E-GEOD-74451 | biostudies-arrayexpress
Project description:The LIM-only protein FHL2 is expressed in SMCs and inhibits SMC-rich lesion formation. However, the underlying mechanism behind FHL2's action in SMCs has been only partially resolved. To further elucidate the role of FHL2 in SMCs we compared the transcriptome of cultured SMCs derived from wild-type (WT) and FHL2-knockout (KO) mice.
2014-10-07 | GSE56860 | GEO
Project description:We examined the RNA expression profiles of whole skin from newborn CRISPR-edited mice that have the 923 enhancer located within the Epidermial Differentiation Complex deleted. We examined two independent deletion lines, 923del and 923large, both homozygous mutants and heterozygotes, as well as wild type mice and involucrin Ivl knockout mice. We find that Ivl, the gene most proximal to 923, is downregulated upon the loss of the enhancer in both independent deletions, and 4 additional genes are also downregulated in both deletion lines, a secondary effect of the loss of Ivl, as concluded by comparing to the Ivl KO mice. We thus conclude that Ivl is the primary target gene of the 923 enhancer and establish a 923-Ivl regulatory module.
2020-10-30 | GSE158869 | GEO
Project description:Transcriptional profiling of human-iPSC derived neurons treated with antimir-edited-miR-376a-3p at site +6 (Anta-E), antimir-native-miR-376a-3p (Anta-N) and scramble (Scr)
2024-01-03 | GSE211696 | GEO
Project description:WS iPSC (iWS780) is a WRN-null iPSC line derived from AG00780 fibroblast. This iPSC line showed normal 46,XY karyotype. iWS780 was gene-edited by CRIPSR/Cas9 to correct the WRN point mutation. Two clones (C21 & C24) were characterized and showed expression of wild-type WRN protein after gene editing. The iPSC lines (isogenic) were subsequently differentiated into mesenchymal stem cells (MSC). RNA-seq was performed on these MSC.
2019-09-24 | GSE137856 | GEO
Project description:To evaluate gene expression changes in response to low-density-lipoprotein related protein 1 (LRP1) depletion in endothelial cells, we performed mRNA-sequencing analysis with microvascular endothelial cells isolated from the liver LRP1 endothelial knockout mice and their littermate control wild type mice.
2021-06-11 | GSE117555 | GEO