ABSTRACT: Gene expression profiling and secretome analysis differentiate Adult-Derived Human Liver Stem/progenitor Cells and human hepatic stellate cells
Project description:Adult-derived human liver stem/progenitor cells (ADHLSC) are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC) derived from the liver non-parenchymal fraction present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. The database include full expression (HGU-219) measurements samples from 7 Adult-Derived Human Liver Stem/progenitor (n=7) and human hepatic stellate samples (n=7)
Project description:Adult-derived human liver stem/progenitor cells (ADHLSC) are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC) derived from the liver non-parenchymal fraction present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity.
Project description:We have established culture systems to generate liver progenitor cells (LPCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) from hiPSCs. Then, we established co-culture system of hiPSC-derived liver cells and performed RNA-seq of hiPSC-derived liver model.
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
Project description:Transcriptome analysis of human induced hepatic progenitor cells (hiHepPCs) in various culture conditions, human liver-derived hepatocytes, human liver-derived cholangiocytes, human umbilical vein endothelial cells (HUVECs), and human peripheral blood-derived endothelial cells (HPBECs) We found that a specific combination of three transcription factors, FOXA3, HNF1A, and HNF6, could convert HUVECs and HPBECs into cells that closely resembled hepatic progenitor cells in vitro. These hiHepPCs were expandable in long-term culture and able to differentiate into hepatocytes and cholangiocytes in accordance with their culture conditions. We conducted RNA-seq analyses to investigate the characteristincs of hiHepPCs and their progenies, in addition to those of parental HUVECs, HPBECs, and human liver-derived cells.
Project description:Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Prooncogenic secretome delivering and trafficking via exosomes is crucial for pre-metastatic microenvironment formation and metastasis. This study aims to explore the underlying molecular mechanisms of how PDAC derived exosomes (Pex) modulate the microenvironments of future sites of metastasis.So we dicided using Hepatic Stellate Cells to see their transcriptomes changing after Pex addition.
Project description:It has been reported that hepatic stellate cells (HSCs) differentiate from mesodermal-derived submesothelial cells during embryonic development, and that these cells express a common surface marker p75 neurotrophin receptor (p75NTR). We sorted p75NTR-expressing cells in embryonic liver at each developmental stage, and transcription profiles were analyzed using the DNA microarray.
Project description:Gene expression of mouse hepatic stellate cells was characterized under the following conditions: Quiescent (isolated from normal mouse liver) and reverted (isolated from mouse liver treated with 4 injections of carbontetrachloride followed by 45 day rest period) Affymetrix Mouse 1.0ST gene expression measurements were used to characterize the transcriptomic basis in quiescent hepatic stellate cells, isolated from normal liver, and reverted hepatic stellate cells, isolated from liver treated with 4 injections of CCl4 followed by a 45 day rest period. Gene expression of mouse hepatic stellate cells was characterized under the following conditions: A. Quiescent control hepatic stellate cells (n=4). B. Reverted hepatic stellate cells (n=4).
Project description:The molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. In addition, the gene expression changes associated with activation of primary human hepatic stellate cells, a key event during fibrogenesis, remain poorly characterized. Here, we provide the transriptomic profile underpinning the healthy phenotype of human hepatocytes, liver sinusoidal endothelial cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as activated HSCs (aHSCs) We assess the transcriptome for purified, non-cultured human hepatocytes, liver sinusoidal cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as culture-activated HSCs (aHSCs).
