Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrated transcriptomic analysis revealed lymphatic-mediated immune dynamics after myocardial infarction

ABSTRACT: Cardiac lymphatic vessels actively regulate immune responses after injury. Intercellular cell adhesion molecule-1 (ICAM-1), a cell surface glycoprotein, extensively expresses in endothelial cells and participates in inflammatory processes by regulating leukocyte recruitment from circulation. However, the specific role of lymphatic endothelial cells (LECs) Icam1 in regulating the immune microenvironment associated with myocardial infarction (MI) remains elusive. In this study, we generated an LEC-specific Icam1 conditional knockout (cko) model and performed single-cell RNA sequencing to evaluate the cellular dynamic features at 3-, 7-, 21-, and 42- days post-MI. Our results showed that Icam1 deletion increased inflammation and fibrosis, indicating aggravated cardiac damage. Our findings indicate that LEC Icam1 might be a potential therapeutic target for improving post-MI outcomes.

ORGANISM(S): Mus musculus

PROVIDER: GSE308860 | GEO | 2025/09/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptional profiling of ex vivo isolated inflammed mouse lymphatic endothelial cells

Project description:Chemokines and adhesion molecules upregulated in lymphatic endothelial cells (LECs) during tissue inflammation are believed to enhance dendritic cell (DC) migration to draining lymph nodes (dLNs), but the in vivo control of this process is not well understood. By performing transcriptional profiling of LECs isolated from murine skin, we found that inflammation induced by a contact hypersensitivity (CHS) response upregulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines in LECs. Furthermore, lymphatic lineage markers like Prox-1, VEGFR3 and LYVE-1 were significantly downregulated during CHS. By contrast, skin inflammation induced by Complete FreundM-bM-^@M-^Ys adjuvant (CFA) induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. In FITC painting experiments, DC migration to dLNs was more strongly increased in CFA- as compared to CHS-induced inflammation. Interestingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 in LECs. However, the requirement for CCR7 signaling became further pronounced during inflammation, whereas CCR7-independent signals only had a minor role in enhancing DC migration. Collectively, these findings indicate that inflammation-induced DC migration is stimulus-dependent and only moderately enhanced by LEC-induced genes other than CCL21. Mouse ear skin single-cell suspensions were prepared by a fast protocol that minimizes the RNA degradation. Fluorescence-activated cell sorting (FACS) was used to sort lymphatic endothelial cells (LEC) from CHS inflammed and control skin. 4 pairs (each with one control and one CHS inflammed sample, sorted and extracted on the same day) of LECs were chosen based on the quality of extracted and amplified material. This gave 8 samples to analyze (4 biological replicates in each condition). Each sample was sorted from 3 mice.

2011-05-19 | E-GEOD-26229 | biostudies-arrayexpress

Transcription profiling of Tbx1 function in adult myocardial infarction hearts [bulk RNA-seq]

Project description:Post-myocardial infarction (Post-MI) heart failure is an unanswered clinical challenge. Current immunological intervention trials to reduce MI damage are unsatisfactory. Tbx1, the major 22q11.2 deletion syndrome (22q11.2DS) disease gene, reactivated in cardiac lymphatic endothelial cells (LECs) to promote post-MI repair. Endothelial deletion of Tbx1 deteriorated post-MI cardiac function. To identify the initial endothelial-derived gene expression changes that are responsible for lymphangiogenesis and cell non-autonomous functions towards immune cells after MI, we enriched CD31+ endothelial cells from 5 dpMI Ctrl and Tbx1cko hearts and performed RNA-seq. In conclusion, our findings revealed that Tbx1 can promote lymphangiogenesis and alleviate excessive cardiac inflammation in post MI hearts.

2023-08-28 | GSE137063 | GEO

The profile of cellular and KSHV microRNAs in KSHV infected lymphatic endothelial cells (6 and 72 hours post infection)

Project description:Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognizable by its distinctive red skin lesions. The lesions are KSHV infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The effects of KSHV infection of LECs were assayed using Affymetrix hgu133plus2 chips at 6 and 72 hours post infection. There were n=4 each of lymphatic endothelial cells (LEC) following 6 hours of culture, LEC following 6 hours post KSHV infection, LEC following 72 hours of culture, and LEC following 72 hours post KSHV infection.

2010-05-18 | E-GEOD-17016 | biostudies-arrayexpress

Single cell RNAseq profiling of Tbx1 function in adult post myocardial infarction hearts [scRNA-seq]

Project description:Post-myocardial infarction (Post-MI) heart failure is an unanswered clinical challenge. Current immunological intervention trials to reduce MI damage are unsatisfactory. Thus a thorough understanding of post-MI immune response is imperative. Tbx1, the major 22q11.2 deletion syndrome (22q11.2DS) disease gene, reactivated in cardiac lymphatic endothelial cells (LECs) to promote post-MI repair. Endothelial deletion of Tbx1 deteriorated post-MI cardiac function through a dual approach, impaired lymphangiogenesis and weakened immunosuppression. To characterize cell autonous function of Tbx1 in endothelial population and cell non-autonous effect in immune cells, we set to performed scRNA-seq on Ctrl (Tbx1flox/flox) and Tbx1cko (Fabp4-Cre;Tbx1flox/flox) hearts. The dataset is comprised of total 55,106 single cells transcriptomes. We identified eight principal non-myocyte types with their known markers, including CD31-expressing vascular endothelial cell (VEC), LEC, pericyte, as well as CD45-expressing monocyte/macrophage, dendritic cell (DC), neutrophil, T/innate lymphoid cell (ILC), and B cell. Interestingly, we found that the relative percentage of monocyte/macrophage population, which is most abundant among all immune cells, was significantly decreased in Tbx1cko hearts, whereas T/ILC population was increased. Taken together, single cell transcriptomic analyses suggest a potential cell non-autonomous effect that Tbx1 deficiency in endothelium may cause imbalance in immune response.

2023-08-28 | GSE136762 | GEO

Transcriptional profiling of ex vivo isolated inflammed mouse lymphatic endothelial cells

Project description:Chemokines and adhesion molecules upregulated in lymphatic endothelial cells (LECs) during tissue inflammation are believed to enhance dendritic cell (DC) migration to draining lymph nodes (dLNs), but the in vivo control of this process is not well understood. By performing transcriptional profiling of LECs isolated from murine skin, we found that inflammation induced by a contact hypersensitivity (CHS) response upregulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines in LECs. Furthermore, lymphatic lineage markers like Prox-1, VEGFR3 and LYVE-1 were significantly downregulated during CHS. By contrast, skin inflammation induced by Complete Freund’s adjuvant (CFA) induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. In FITC painting experiments, DC migration to dLNs was more strongly increased in CFA- as compared to CHS-induced inflammation. Interestingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 in LECs. However, the requirement for CCR7 signaling became further pronounced during inflammation, whereas CCR7-independent signals only had a minor role in enhancing DC migration. Collectively, these findings indicate that inflammation-induced DC migration is stimulus-dependent and only moderately enhanced by LEC-induced genes other than CCL21.

2011-05-20 | GSE26229 | GEO

Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury

Project description:Background: The inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Methods: Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI 72 hours post injury. Data was processed using the Seurat package. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation in in vitro human LECs. Results: We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved in endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models were also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. Conclusions: In this study, we uncover lymphatic vessel structural features of captured populations and injury-induced genetic changes. We further determine LEC gene expression is altered between injury models. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.

2024-02-20 | GSE236199 | GEO

Profiling of filarial induced genes in lymphatic endothelial cells

Project description:To observe the global changes in the lymphatic endothelial cells upon exposure to filarial antigens or parasites, LECs were stimulated for 24, 48, and 72hrs and the expression profiles were carried out. Human filarial parasites Brugia malayi and Wuchereria bancrofti habitat the lymphatics and cause lymphatic dilatation and lymphedema. In order to evaluate the effect of various stage specific effects on the lymphatic endothelial cells (LEC) and understand how they modulate the lymphatic dysfunction, LECs were stimulated in antigens derived from the Brugia malayi. These are preliminary time course data towards understanding how the filarial antigens induce lymphangiogenesis.

2010-05-19 | E-GEOD-15454 | biostudies-arrayexpress

Transcriptomic characterization of cardiac LECs and macrophages isolated from ACKR3∆Lyve1 and wild type mice with or without LAD ligation

Project description:In our study, we detected activation of ACKR3 signaling in cardiac lymphatics adjacent to the site of ischemic injury of left anterior descending artery (LAD) ligation. Furthermore, we found that Ackr3∆Lyve1 mice exhibited better survival and were protected from the formation of acute tissue edema after ischemic cardiac injury, in addition to a denser cardiac lymphatic network after LAD ligation, especially in the injured tissues. To characterize the transcriptomic changes in cardiac lymphatic endothelial cell (LEC) and macrophage populations in the heart upon ischemic cardiac injury in Ackr3∆Lyve1 mice, CD68+ macrophages and CD68-/LYVE1+ LECs were immunoprecipitated from the ventricles of Ackr3fl/fl and Ackr3∆Lyve1 mice at baseline or 7 days post LAD ligation. We then performed microarray on the collected lymphatic and macrophage RNA samples.

2025-03-28 | GSE289143 | GEO

Transcription profiling of human lymphatic endothelial cells, mouse dermal cells and human skin cells reveals an inflammation-induced mechanism for leukocyte transmigration of lymphatic vessel endothelium.

Project description:The exit of antigen-presenting cells (APC) and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels is however unknown. Here we show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LEC) leading to expression of the key leukocyte adhesion receptors ICAM-1, VCAM-1 and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of DC via afferent lymphatics. Lastly, we show that TNF_-stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking mAbs. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for anti-inflammatory therapy. Experiment Overall Design: Global gene expression profile of normal dermal lymphatic endothelial cells cultured in media alone (no TNF) compared to that of normal dermal lymphatic endothelial cells stimulated with TNFalpha, 1 ng/ml for 48h.Triplicate biological samples were analyzed from human lymphatic endothelial cells (3 x controls; 3 x TNF treated) and a single sample analyzed from mouse lymphatic endothelial cells (1 x controls; 1 x TNF treated).

2008-11-07 | E-GEOD-6257 | biostudies-arrayexpress

Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture

Project description:<p>Breast cancer metastasis occurs via blood and lymphatic vessels. Breast cancer cells 'educate' lymphatic endothelial cells (LECs) to support tumor vascularization and growth. However, despite known metabolic alterations in breast cancer, it remains unclear how lymphatic endothelial cell metabolism is altered in the tumor microenvironment and its effect in lymphangiogenic signaling in LECs. We analyzed metabolites inside LECs in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using 1H nuclear magnetic resonance (NMR) metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk. LECs co-cultured with breast cancer cells exhibited cell-line dependent altered metabolic profiles, including significant changes in lactate concentration in breast cancer co-culture. Cell metabolic phenotype analysis using Seahorse showed LECs in co-culture exhibited reduced mitochondrial respiration, increased reliance on glycolysis and reduced metabolic flexibility. Optical redox ratio measurements revealed reduced NAD(P)H levels in LECs potentially due to increased NAD(P)H utilization to maintain redox homeostasis. 13C-labeled glucose experiments did not reveal lactate shuttling into LECs from breast cancer cells, yet showed other 13C signals in LECs suggesting internalized metabolites and metabolic exchange between the two cell types. We also determined that breast cancer co-culture stimulated lymphangiogenic signaling in LECs, yet activation was not stimulated by lactate alone. Increased lymphangiogenic signaling suggests paracrine signaling between LECs and breast cancer cells which could have a pro-metastatic role.</p>

2024-06-25 | MTBLS859 | MetaboLights

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data