Project description:Inactivation of BMP9/10 in mice leads to attenuated contractility of smooth muscle cells and decreased blood pressure.Treatment of de-differentiated PASMCs with BMP9/10 resulted in a strong increase of ACTA2 expression as measured by immunofluorescence and RT-PCR, indicating a switch from the de-differentiated, synthetic to a differentiated, contractile state. To further study the role of BMP9/10 in smooth muscle cells, we isolate PSAMCs and stimulate cells with or without BMP9/10 and perform the RNA-seq analysis.
Project description:Aorta was isolated from ANF-Cre positive/BMP10 loxP/loxP/BMP9-/- (BMP9/10 dKO) mice. ANF-Cre negative BMP10 loxP/loxP mice were used as controls. Transcritional profiling was performed to understand the impact of BMP9/10 expression on aorta function.
Project description:To identify potential biological targets of the TGFβ pathway involved in AVM formation, we performed ChIP-sequencing experiments on BMP9 stimulated Ms1 endothelial cells (ECs). This data provides a comprehensive list of all SMAD4 binding sites in endothelial cells.
Project description:The liver is a largest solid organ in the body and is majorly composed of HCs, ECs, KCs, and HSCs, which spatially interact and cooperate each other to maintain liver homeostasis. However, the complexity and molecular mechanisms underlying the crosstalk between these different cell types remain to be revealed. Here, we generated mice with conditional deletion of Bmp9/10 in different liver cell types and demonstrated that HSCs was the major source of BMP9 and BMP10 in the liver. Using transgenic ALK1 (receptor for BMP9/10) reporter mice, we found that ALK1 is expressed on KCs and ECs other than HCs and HSCs. KCs from Bmp9/10HSC-KO (conditional deletion of Bmp9/10 from HSCs) mice lost their signature genes expression, such as ID1/3, CLEC4F, VSIG4 and CLEC2, and were replaced by monocyte-derived macrophages. ECs from Bmp9/10HSC-KO mice also lost their identity and were transdifferentiated to continuous ECs, ultimately leading to collagen IV deposition and liver fibrosis. Hepatic ECs expressed several angiocrine factors, such as BMP2, BMP6, Wnt2 and Rspo3, to regulate liver iron metabolism and metabolic zonation. We found that these angiocrine factors were significantly decreased in ECs from Bmp9/10HSC-KO mice, which further resulted in liver iron overload and disruption of HCs zonation. In addition, focal fatty liver spontaneously occurred in Bmp9/10HSC-KO mice at the age of 28W. In summary, we demonstrated that HSCs play a central role in mediating liver cell-cell crosstalk via production of BMP9/10 to maintain liver health.
Project description:Aorta was isolated from ANF-Cre positive / BMP10 loxP/loxP / BMP9-/- (BMP9/10 dKO) mice. ANF-Cre negative BMP10 loxP/loxP mice were used as controls. Transcriptional profiling was performed to understand the importance of BMP9/10 expression on aorta function.
Project description:This experiment was desinged to investigate the difference in global gene expression induced by the circulating form of BMP9, pro-BMP9, and BMP9 in complex with soluble endoglin (sENG:BMP9).
Project description:HUVEC were left untreated or stimulated for 5h with 2 ng/ml TNF. Comparsion of the gene profiles revealed TNF-mediated gene expression changes in HUVEC. Keywords: parallel sample
