Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA533227 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8921370.fastq.gz | Fastqsanger.gz | |||
| SRR8921371.fastq.gz | Fastqsanger.gz | |||
| SRR8921372.fastq.gz | Fastqsanger.gz | |||
| SRR8921373.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded.
2019-04-18 | GSE129933 | GEO
Project description:Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded.
| S-EPMC6530422 | biostudies-literature
Project description:Tissue lymphatic vessels network plays critical roles in immune surveillance and tissue homeostasis in response to pathogen invasion, but how lymphatic system per se is remolded during infection is less understood. Here, we observed that influenza infection induces a significant increase of lymphatic vessel numbers in the lung, accompanied with extensive proliferation of lymphatic endothelial cells (LECs). Single-cell RNA sequencing illustrated the heterogeneity of LECs, identifying a novel PD-L1+ subpopulation that is present during viral infection but not at steady state. Specific deletion of Pd-l1 in LECs elevated the expansion of lymphatic vessel numbers during viral infection. Together these findings elucidate a dramatic expansion of lung lymphatic network in response to viral infection, and reveal a PD-L1+ LEC subpopulation that potentially modulates lymphatic vessel remolding.
2024-05-06 | GSE266192 | GEO
Project description:This study aims to determine changes in transcriptomic profiles in lymphatic vessels in response to ischemia-reperfusion injury, which mimics conditions in liver transplantation. This experiment will determine the potential role of lymphatic vessels during the ischemia-reperfusion injury in the liver.
2024-08-19 | GSE255346 | GEO
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.
2021-03-01 | GSE158988 | GEO
Project description:While colorectal cancer liver metastasis (CRCLM) is major cause of death of colorectal cancer, the mechanism of intrahepatic dissemination (trans-lymphatic metastasis) is not fully elucidated. Lymphangiogenesis can be the mechanism of the dissemination, but there are few evidences to prove it. In this study, we attempted to clarify the mechanism using syngeneic murine CRCLM model, especially focusing on vascular endothelial growth factor C (VEGFC), a promoter of lymphangiogenesis. We confirmed that 1) intrahepatic metastasis of CRCLM via lymphatic vessels was seen and lymphangiogenesis was upregulated in the CRCLM-bearing liver, 2) the degree of lymphangiogenesis and CRCLM was significantly correlated with the expression of VEGFC in colorectal cancer (CRC) cells and 3) macrophage inflammatory protein-1α (MIP-1α) was released from CRC cells under the stimulation of VEGFC and induced migration of immature bone marrow derived cells into the liver and differentiation into macrophage, which promoted dissemination of CRCLM. These findings suggest the possibility of therapeutic strategy targeting VEGFC / MIP-1α for diminishing CRCLM. In conclusion, VEGFC in CRC cells promoted trans-lymphatic metastasis of CRCLM by upregulation of lymphangiogenesis directly and indirectly via induction of macrophages derived from bone marrow cells.
2018-09-30 | GSE113235 | GEO
Project description:Oxidized Low-Density Lipoprotein drives dysfunction of the liver lymphatic system
| PRJNA659994 | ENA
Project description:We developed a large animal model, with clinically relevant gravitational loading on the lymphatic vasculature, that enables longitudinal tracking of lymphatic function in vivo as well as end-point analysis of vessel function and mechanics. One of two parallel lymphatic vessels in the sheep hind limb was ligated with the contralateral limb acting as an internal control. To determine the changes in the protein expression profiles in the lymphatic muscle cells from the remodeled vessel compared to the control, we expanded isolated LMC in vitro and performed bottom-up proteomic analysis using a Q Exactive Plus mass spectrometer. Label-free quantitative (LFQ) methods directly used the raw spectral data from parallel MS runs to determine relative protein abundances. We used both “MS/MS (MS2) spectral counting” and “precursor MS1 area” methods for label free quantitation and further contrasting the differentially expressed proteomic profiles across the control and remodeled lymphatic muscle samples to determine the alterations in mitochondrial dysfunction and elevated oxidative stress within the lymphatic muscle.
2021-01-12 | PXD014343 | Pride
Project description:In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we investigated the lymphatic draining function at the tibial fracture sites using near-infrared indocyanine green lymphatic imaging (NIR-ICG) and discovered that lymphatic drainage insufficiency (LDI) started on day one and persisted for up to two weeks following the fracture. Sufficient lymphatic drainage facilitates fracture healing. Furthermore, we identified that lymphatic platelet thrombosis (LPT) blocked the draining lymphoid sinus and LVs, caused LDI, and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage decreased neutrophils and increased M2-like macrophages of the hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). Lymphatic platelet thrombolysis also benefits senile fracture healing. These findings demonstrate that LPT limits bone regeneration by impeding lymphatic transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone repair.
2024-10-05 | PXD056584 |
Project description:Complex lymphatic anomalies (CLAs) are sporadically occurring diseases caused by the maldevelopment of lymphatic vessels. We and others recently reported that somatic activating mutations in KRAS can cause CLAs. However, the mechanisms by which activating KRAS mutations cause CLAs are poorly understood. Here we show that KRASG12D expression in lymphatic endothelial cells (LECs) during embryonic development impairs the formation of lymphovenous valves and causes the enlargement of lymphatic vessels. We demonstrate that KRASG12D expression in primary human LECs induces cell spindling, proliferation, and migration. It also increases AKT and ERK1/2 phosphorylation and decreases the expression of genes that regulate lymphatic vessel maturation. We show that MEK1/2 inhibition with the FDA-approved drug trametinib suppresses KRASG12D-induced morphological changes, proliferation, and migration. Trametinib also decreases ERK1/2 phosphorylation and increases the expression of genes that regulate the maturation of lymphatic vessels. We also show that trametinib and Cre-mediated expression of a dominant-negative form of MEK1 (Map2k1K97M) suppresses KRASG12D-induced lymphatic vessel hyperplasia in embryos. Last, we demonstrate that conditional knockout of wild-type Kras in LECs does not affect the formation or function of lymphatic vessels. Together, our data indicate that KRAS/MAPK signaling must be tightly regulated during embryonic development for the proper development of lymphatic vessels and further support the testing of MEK1/2 inhibitors for treating CLAs.
2023-09-25 | GSE239737 | GEO