Transcriptome comparsion of HB-orgs/P-heporgs cultured under static (HB-S/hep-S) or dynamic (HB-D/hep-D) conditions
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE265845 | GEO | 2025/07/16
REPOSITORIES: GEO
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Project description:Transcriptome comparsion of HB-orgs/P-heporgs cultured under static (HB-S/hep-S) or dynamic (HB-D/hep-D) conditions
| PRJNA1104529 | ENA
Project description:Background & Aims: The increasing requirements for hepatocytes in therapeutics and pharmacy call for an efficient system that enables large-scale production of functional hepatocytes in vitro. Hepatoblast (HB) hold the ability to regenerate liver when damaged, combined with organoid (org) technology, the culture of human pluripotent stem cell (hPSCs) derived HB-orgs was established under 2D culture system, enabling long-term expansion of HB in vitro. However, the expensive cost and the limitation of existing methods impede the further scale up of the production. Methods: Under 3D suspension culture conditions with the support of Matrigel at low concentration in conjunction with employing the developed (defined) medium, we developed a novel system to efficiently and reproducibly generate expandable HB-orgs and functional polarized hepatocyte organoids (P-hep-orgs) derived from hESCs. HB-orgs were further scaled up by dynamic culture in spinner flasks, and the maturity and function of P-hep-orgs was validated by transcriptome analysis and in vitro and in vivo hepatic functional assays. scRNA-seq was used to further profile HB-orgs and P-hep-orgs. Results: Our HB-orgs exhibited biopotency that could differentiate into functional hepatocytes and cholangiocytes. They proliferated actively at least for 15 passages with defined medium through avoiding the excessive autophagy under 3D suspension culture condition. HB-orgs showed higher proliferation rate in dynamic culture conditions and could reach 10^12 cell number at the initiate number of 3 million cells in only 4 weeks. With further differentiation, P-hep-orgs displayed characteristics of hepatocytes in liver, including the polarization state which mediated by integrin-AMPK signalling pathway, molecular features and improved liver functions. Moreover, P-hep-orgs were used for predicting the toxicity of various compounds, and modeling the development of hepatic lipid accumulation, as well as rescuing acute liver failure of mice. Conclusion: Our work provided a cost-efficient method for large-scale generation of 3D HB-orgs and 3D P-hep-orgs that hold considerable potential to be a robust platform for disease research, drug screening/development and toxic study, as well as clinical applications.
2024-12-30 | GSE239550 | GEO
Project description:The increasing requirements for hepatocytes in therapeutics and pharmacy call for an efficient system that enables large-scale production of functional hepatocytes in vitro. We developed a method to obtain HB-orgs and mature P-hep-orgs from hPSCs under 3D suspension culture system. HB-orgs showed bipotency and proliferate capacity, and P-hep-orgs exhibited hepatic polarization and mature hepatic functions. Single cell RNAseq was used to further profile HB-orgs and P-hep-orgs.
2024-12-30 | GSE240097 | GEO
Project description:Idiomarina sp. HB strain:HB Genome sequencing
| PRJNA1057588 | ENA
Project description:The mammalian liver possesses a remarkable regenerative ability. 1) The 'oval cell' response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. 2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). We establish a long-term 3D organoid culture system from mouse and human fetal/pediatric/adult hepatocytes that retain key morphological and functional features of hepatocytes fate. We report the mRNA and single cell sequencing of Hep-Orgs from different donors in different passages. We compared Hep-Orgs with primary hepatocytes, proliferative hepatocytes or Chol-Orgs derived from Epcam+ biliary cells. By analyzing, we determine similar gene expression profile of Hep-Orgs with primary hepatocytes and make genes lists distinguished with undamaged hepatocytes as well. We find the Hep-Orgs resemble proliferative damage-response of hepatocytes after partial hepatectomy while Chol-Orgs express high cholangiocytes markers. The sequencing data constitutes a valuable resource to understand liver organoids especially Hep-Orgs.
2018-11-29 | GSE111301 | GEO
Project description:Due to the widespread application of food-relevant inorganic nanomaterials, the gastrointestinal tract is potentially exposed to these materials. Gut-on-chip in vitro model systems are proposed for the investigation of compound toxicity as they better recapitulate the in vivo human intestinal environment than static models, due to the added shear stresses associated with the flow of medium in line with what cells experience in vivo. We aimed to compare the cellular responses of intestinal epithelial Caco-2 cells at the gene expression level upon TiO2 (E171) and ZnO (NM110) nanomaterial exposure when cultured under dynamic and static conditions. For this, we applied whole genome transcriptome analyses. Differentially expressed genes and related biological processes revealed culture condition specific responses upon exposure to TiO2 and ZnO nanomaterials. The materials had more effects on cells cultured in the gut-on-chip when compared to the static model, indicating that shear stress might be a major factor in cell susceptibility. This is the first report on application of a gut-on-chip system to evaluate cellular responses upon TiO2 and ZnO nanomaterials compared to a static system and extends current knowledge on nanomaterial-cell interactions and toxicity assessment. Dynamically cultured cells appear to be more sensitive and the gut-on-chip might thus be an attractive model to be used more extensively in the toxicological hazard characterization.
2022-01-26 | GSE158620 | GEO
Project description:Hepatoblastoma (HB) is the most common liver cancer in children, but few pre-treatment tumors have been molecularly profiled. Consequently, there are no validated prognostic or therapeutic biomarkers for HB patients. We report on molecular analysis of 88 clinically-annotated HB tumors. This analysis pointed to three risk-stratifying molecular subtypes—low, intermediate and high risk—that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways. High-risk tumors are characterized by high NFE2L2 activity and LIN28B, HMGA2, SALL4 and AFP expression, low let-7 expression and HNF1A activity, and high coordinated expression of oncofetal proteins and stem cell markers. Tests on a 35 HB validation set supported these genes as prognostic biomarkers.
2016-10-10 | GSE75271 | GEO
Project description:Hepatoblastoma (HB) is the most common liver cancer in children, but few pre-treatment tumors have been molecularly profiled. Consequently, there are no validated prognostic or therapeutic biomarkers for HB patients. We report on molecular analysis of 88 clinically-annotated HB tumors. This analysis pointed to three risk-stratifying molecular subtypes—low, intermediate and high risk—that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways. High-risk tumors are characterized by high NFE2L2 activity and LIN28B, HMGA2, SALL4 and AFP expression, low let-7 expression and HNF1A activity, and high coordinated expression of oncofetal proteins and stem cell markers. Tests on a 35 HB validation set supported these genes as prognostic biomarkers.
2017-01-30 | GSE75284 | GEO