Project description:We report a novel technique to reprogram human fibroblasts into endothelial and smooth muscle cells using partial iPSC reprogramming and chemically defined media. Using appropriate media conditions for differentiation of human pluripotent cells to CD34+ vascular progenitor cells, we show that temporary expression of pluripotent transcription factors and treatment with chemically-defined media, will induce differentiation of human fibroblasts to CD34+ vascular progenitor cells. Sorted CD34+ cells can then be directed to differentiate into vascular endothelial cells expressing a variety of smooth muscle markers. We have assessed the global DNA methylation (Illumina Infinium HD 450K DNA methylationBeadChips) and transcriptional (Illumina HT12v4 Gene Expression Bead Array) profiles of transdifferentiated endothelial cells and smooth muscle, human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC) differentiated CD34+ angioblasts, hESCs, hiPSC, primary smooth muscle and primary human umbilical vein endothelial cells using microarrays.
Project description:We report a novel technique to reprogram human fibroblasts into endothelial and smooth muscle cells using partial iPSC reprogramming and chemically defined media. Using appropriate media conditions for differentiation of human pluripotent cells to CD34+ vascular progenitor cells, we show that temporary expression of pluripotent transcription factors and treatment with chemically-defined media, will induce differentiation of human fibroblasts to CD34+ vascular progenitor cells. Sorted CD34+ cells can then be directed to differentiate into vascular endothelial cells expressing a variety of smooth muscle markers. We have assessed the global DNA methylation (Illumina Infinium HD 450K DNA methylationBeadChips) and transcriptional (Illumina HT12v3 and HT12v4 Gene Expression Bead Array) profiles of transdifferentiated endothelial cells and smooth muscle, human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC) differentiated CD34+ angioblasts, hESCs, hiPSC, primary smooth muscle and primary human umbilical vein endothelial cells using microarrays.
Project description:Rapid regeneration of smooth muscle after vascular injury is essential for maintaining proper artery function. The current view holds that pre-existing smooth muscle proliferate and expand in responding to vascular injury, contributing to virtually all new smooth muscle cells. Whether resident vascular stem cells for smooth muscle exist remains controversial and their putative functional role for artery repair and regeneration is elusive. Here we performed cell fate mapping and single cell RNA sequencing to identify Sca1+ vascular stem cells (VSCs) residing in the adventitial layer of artery wall.
Project description:Vascular smooth muscle cell plasticity plays a pivotal role in the pathophysiology of vascular diseases. Despite compelling evidence demonstrating the importance of transcription factor GATA6 in vascular smooth muscle, the functional role of GATA6 remains poorly understood. The aim of this study was to elucidate the role of GATA6 on cell migration and to gain insight into GATA6-sensitive genes in smooth muscle. Therefore, we performed Affymetrix microarray analysis on human coronary artery smooth muscle cells after overexpressing GATA6 by adenovirus transduction and compared it to control which are cell transduced with Ad-CMV-null.
Project description:The moderate response of smooth muscle cells is beneficial to the repair of vascular injury, while the continuous exposure of intravascular growth factors, and other stimulating factors will cause the dysfunction of smooth muscle cells, leading to the pathological remodeling of blood vessels, which is called neointimal hyperplasia. The aim of this study is to investigate the biological function of PTPN14 in vascular smooth muscle cells (VSMCs) and the mechanism of PTPN14 in regulating neointimal hyperplasia.
Project description:Analysis of hypoxia-exposed human pulmonary artery smooth muscle cells to identify the commonly regulated genes by hypoxia. Results provide insight into the regulatory mechanism of hypoxic responses in vascular smooth muscle cells.
Project description:Analysis of hypoxia-exposed human pulmonary artery smooth muscle cells to identify the commonly regulated microRNAs by hypoxia. Results provide insight into the regulatory mechanism of hypoxic responses in vascular smooth muscle cells.
Project description:Our goal is to study the contribution of endothelial, smooth muscle, and macrophage gene expression to early atherosclerosis using vessels from healthy, pre-lesioned, and lesioned mice. To accomplish this, we developed a method to isolate endothelial cells directly from the aorta and quantitate transcripts in RNA isolated from these cells. We performed expression array analysis on RNA isolated directly from the vascular cells of individual control, pre-lesioned, and atherosclerotic mouse aortas. Array expression analysis was not performed on smooth muscle cells or macrophages.
Project description:Platelet-derived growth factor (PDGF) signalling and the subsequent activation of the calcium ion channel, ORAI1 are critical drivers of pathological remodelling of native vascular smooth muscle cells to proliferative state, which is a process associated with various vascular diseases. This study aims to reveal transcriptional networks altered following ORAI1 inhibition in vascular smooth muscle cells. To study the effect of ORAI1 inhibition on VSMC biology, we performed RNA-Seq analysis of PDGF-stimulated primary human aortic smooth muscle cells treated with either ORAI1 inhibitor, (n=4) or with vehicle (n=4), and investigated the effect of ORAI1 inhibition on the transcriptional response of cells.