Expression data comparing TMNK-1 to HMEC
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE60776 | GEO | 2014/12/01
SECONDARY ACCESSION(S): PRJNA259528
REPOSITORIES: GEO
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2022-09-06 | PXD029241 | Pride
Project description:Chronic liver disease is a major leading cause of portal hypertension that affects approximately 1.5 billion people globally. We show that GIMAP5, a small organellar GTPase, is selectively expressed in liver endothelial cells and human GIMAP5 deficiency causes portal hypertension with capillarization of liver sinusoidal endothelial cells (LSECs). LSEC capillarization is recapitulated in GIMAP5 loss-of-function (LOF) mice, and upon conditional Gimap5 deletion in endothelial cells. Single cell RNA-sequencing analyses reveals replacement of LSECs with capillarized endothelial cells and expansion of liver lymphatic endothelial cells in GIMAP5 LOF mice, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC-specification. Our studies reveal that GIMAP5 prevents portal hypertension by maintaining LSEC identity and suggest that LSEC is an induced endothelial cell state.
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Project description:The distinction between lymphatic and blood vessels is biologically fundamental. Two immortalized cell lines, which have been widely used as models for endothelial cells of blood vascular origin, are the human microvascular endothelial cell line-1 (HMEC-1) and the telomerase-immortalized microvascular endothelial cell line (TIME). However, analysis of protein expression by flow cytometry revealed expression of lymphatic markers on these cell lines. Furthermore, functional in vitro leukocyte transmigration assays demonstrated deficiencies in several steps of the leukocyte extravasation cascade. Hence we performed this microarray analysis of the gene expression in HMEC-1 and TIME. We then compare the expression profiles to those of published blood- and lymphatic endothelial cells.
2013-09-11 | GSE42216 | GEO
Project description:The distinction between lymphatic and blood vessels is biologically fundamental. Two immortalized cell lines, which have been widely used as models for endothelial cells of blood vascular origin, are the human microvascular endothelial cell line-1 (HMEC-1) and the telomerase-immortalized microvascular endothelial cell line (TIME). However, analysis of protein expression by flow cytometry revealed expression of lymphatic markers on these cell lines. Furthermore, functional in vitro leukocyte transmigration assays demonstrated deficiencies in several steps of the leukocyte extravasation cascade. Hence we performed this microarray analysis of the gene expression in HMEC-1 and TIME. We then compare the expression profiles to those of published blood- and lymphatic endothelial cells. Analysis of the gene expression profile of the immortalized human endothelial cell lines HMEC-1 and TIME to be compared to published primary blood- and lymphatic endothelial cells (see supplementary file linked below).
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Project description:Coagulation Factor VIII (FVIII) plays a pivotal role within the coagulation cascade, and deficiencies in its levels, as seen in Hemophilia A, can lead to significant health implications. Liver sinusoidal endothelial cells (LSECs) are the main producers and contributors of FVIII in blood, a fact we have previously elucidated through mRNA expression profiling when comparing these cells to other endothelial cell types. Our current investigation delves into small microRNAs, analyzing their distinct expression patterns across various endothelial cells and hepatocytes. The outcome of this exploration underscores the discernible microRNA expression differences that set LSECs apart from both hepatocytes (193 microRNAs at p < 0.05) and other endothelial cells (72 microRNAs at p < 0.05). Notably, the 134 and 35 overexpressed microRNAs in LSECs compared to hepatocytes and other endothelial cells, respectively, shed light on the unique functions of LSECs in the liver. Our investigation identified a panel of 10 microRNAs (miR-429, miR-200b-3p, miR-200a-3p, miR-216b-5p, miR-1185-5p, miR-19b-3p, miR-192-5p, miR-122-5p, miR-30c-2-3p, and miR-30a-5p) that distinctly define LSEC identity. Furthermore, our scrutiny extended to microRNAs implicated in F8 regulation, revealing a subset - miR-122-5p, miR-214-3p, miR-204-3p, and miR-2682-5p - whose expression intricately correlates with F8 expression within LSECs. This microRNA cohort emerges as a crucial modulator of F8, both directly through suppression and indirect effects on established F8-related transcription factors. The above miRNA emerged as potential targets for innovative therapies in Hemophilia A patients.
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Project description:BMP6 is an iron-sensing cytokine produced by liver sinusoidal endothelial cells (LSECs). The transcription factor NRF2 was proposed to induce Bmp6 expression in response to iron-triggered oxidative stress, and NRF2 knock-out mice were shown not capable of regulating Bmp6 in response to massive diet-imposed iron overload. However, LSEC Bmp6 expression levels in the hemochromatosis mouse model reflect hepatocytic, not endothelial iron content. Hence, it is not fully resolved how iron signals translate into alterations of Bmp6 mRNA levels. To further explore the mechanisms of Bmp6 regulation, we employed female mice aged 10-11 months that are hallmarked by hepatocytic, but not LSEC iron accumulation and decreased transferrin saturation, hinting at the absence of systemic iron overload. We found that LSECs of aged mice exhibit increased Bmp6 levels as compared to young controls, but do not show oxidative stress or a transcriptional signature characteristic of activated NFR2-mediated signaling in FACS-sorted LSECs. We further observed that primary murine LSECs derived from both wild-type and NRF2 knock-out mice induce Bmp6 in response to acute iron exposure. By analyzing RNA sequencing data of FACS-sorted LSECs from aged versus young mice, as well as upon acute injections of iron citrate in young mice, we identified ETS1 as a candidate transcription factor involved in Bmp6 regulation. By conducting siRNA-mediated knock-down and small-molecule treatments in primary LSECs, we show that Bmp6 transcription is regulated in an NRF2-independent manner via ETS1, which is activated downstream of p38 MAP kinase-mediated signaling. This knowledge expands the understanding of Bmp6 transcriptional control in both iron-triggered oxidative stress and under the conditions uncoupled to LSECs reactive oxygen species levels.
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