A cell atlas of the regenerating human liver after portal vein embolization
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ABSTRACT:
PROVIDER: PRJEB59716 | ENA |
REPOSITORIES: ENA
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Project description:In this work, we applied single-cell transcriptome sequencing on primary human liver tissue samples to study cellular processes underlying human liver regeneration. In order to study regeneration-specific cellular processes we obtained primary healthy liver tissue samples and liver tissue samples from patients that underwent a preoperative medical procedure called portal vein embolization (PVE). This medical treatment is performed to enlarge part of the liver such that a diseased portion can be removed avoiding liver insufficiency and thus we used post-PVE-derived tissues as a model to study liver regeneration in humans. This paradigm enabled us to catalog cell states related to tissue structure in two important and physiologically relevant conditions: hypertrophy and atrophy. In addition, we overcame technical challenges and provided novel protocols and pipelines for generating high quality liver cell atlases from frozen specimens showing consistency in results between fresh and frozen tissue datasets. Moreover, we established tissue-scale iterative indirect immunofluorescence imaging to enable high-dimensional spatial analysis of perivascular microenvironments and uncover cellular and histological alterations to regenerating liver lobules.
2024-04-13 | E-MTAB-12594 | biostudies-arrayexpress
Project description:The hypothesis is that liver venous deprivation (LVD) could strongly improve hypertrophy of the future remnant liver (FRL) at 3 weeks, as compared to portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.
| 2297214 | ecrin-mdr-crc
Project description:RATIONALE: Embolization blocks blood flow to part of an organ and/or tumor. Blocking the portal vein on one side of the liver may cause the opposite side of the liver to increase in size and decrease the risk of liver failure following surgery.
PURPOSE: Phase II trial to study the effectiveness of portal vein embolization in treating patients who have liver metastases from primary colorectal cancer.
| 2007016 | ecrin-mdr-crc
Project description:Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation. Characterization of the transcriptome of fetal liver and adult bone marrow niche using RNA-seq
2015-12-03 | E-GEOD-72341 | biostudies-arrayexpress
Project description:Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation.
2015-12-03 | GSE72341 | GEO
Project description:Interventions: One group:portal vein embolization approach-recanalization of the umbilical vein
Primary outcome(s): Portal vein catheter success rate
Study Design: historical control
| 2668806 | ecrin-mdr-crc
Project description:Persistent liver injury triggers a fibrogenic program that causes pathologic remodelling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and regression remain understudied. Here, we generated hepatic transcriptome profiles in two well-established liver disease models at peak fibrosis and during spontaneous regression after the removal of the inducing agents. We linked the dynamics of key liver disease readouts, such as portal pressure, collagen proportionate area, and transaminase serum levels, to most differentially expressed genes, enabling the identification of transcriptomic signatures of progressive vs. regressive liver fibrosis and portal hypertension. These candidate biomarkers (e.g., Scube1, Tcf4, Src, Hmga1, Trem2, Mafk, Mmp7) were also validated in RNA-seq datasets of patients with cirrhosis and portal hypertension. Finally, deconvolution analysis identified major cell types and suggested an association of macrophage and portal hepatocyte signatures with portal hypertension and fibrosis area in both models.
2024-02-13 | E-MTAB-13804 | biostudies-arrayexpress
Project description:We compared transcriptomic profiles of hepatic macrophages between sham operated rats, rats 3 days and 10 days after partial portal vein ligation (PPVL) surgery (n=3). The number of genes with a significant change was most numerous in Sham vs 3 days, followed by Sham vs 10 days and 3 days vs 10 days.
2019-01-01 | GSE117467 | GEO
Project description:Surgical resection has offered the best option for prolonged survival in patients with colorectal liver metastases. Limiting factor for major liver resections is the size of the future liver remnant (FLR). In case of normal liver function, 30% of the total liver volume is considered to be sufficient to maintain adequate liver function after resection. In an attempt to further increase "resectability" criteria for patients with too small FLR surgical and interventional maneuvers such as portal vein embolization and portal vein ligation in two-stage hepatectomies have been implemented, but they need an interval of 4-8 weeks to achieve sufficient hypertrophy. In order to obtain adequate but rapid parenchymal hypertrophy a new surgical two-step technique, ALPPS, was introduced for oncological patients requiring extended hepatic resection with limited functional reserve. Both procedures can be performed with acceptable morbidity and mortality.
The investigators conclude that it is time to perform a randomized study comparing the two surgical approaches in regard to oncological outcome.
| 2214133 | ecrin-mdr-crc
Project description:Gut-derived microbial metabolites have been shown to play key roles in human physiology and disease. However, establishing mechanistic links between gut microbial metabolites and disease pathogenesis in animal models presents many challenges. The major route of absorption for microbe-derived small molecules is venous drainage via the portal vein to the liver. In the event of extensive liver first pass- or presystemic hepatic metabolism, the route of administration of these metabolites becomes critical. Here we describe a novel portal vein cannulation technique using a subcutaneously implanted osmotic pump to achieve continuous portal vein infusion in mice. First, the microbial metabolite trimethylamine (TMA) was administered over 4 weeks and compared to a vehicle control. Using a liquid chromatography-tandem mass spectrometry (LC-MS/MS), an increase in peripheral plasma levels of TMA and its host liver-derived co-metabolite trimethylamine-N-oxide (TMAO) were observed in a sexually-dimorphic manner. Next, 4-hydroxyphenylacetic acid (4-HPAA), a structurally-distinct microbial metabolite that undergoes extensive hepatic first pass metabolism, was administered portally to examine its effects on hepatic gene expression. Peripheral plasma levels showed no difference in free or total 4-HPAA. However, while liver tissue demonstrated no difference in free 4-HPAA, total levels were increased when compared to the control group. More importantly, significant changes were observed in hepatic gene expression using an unbiased RNA sequencing approach. Collectively, this work describes a novel method for administering gut microbe-derived metabolites via the portal vein, mimicking their physiologic delivery in vivo.
2021-05-10 | GSE159775 | GEO