Modeling metabolic-associated steatohepatitis with human pluripotent stem cell-derived liver organoids DOI Creative Commons
Xiaoshan Wu, Dacheng Jiang, Yuchen Wang

et al.

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(12)

Published: Nov. 29, 2024

Background: Metabolic-associated steatohepatitis (MASH) is one of the most prevalent liver diseases worldwide, with a global prevalence estimated between 3% and 5%, posing significant health burden. Human organoids (HLOs) have previously been generated to model steatohepatitis, offering potential cellular disease for studying MASH. However, current HLO lacks detailed molecular characterizations requires further improvement. Methods: HLOs derived from human pluripotent stem cells were treated oleic acid TGFβ mimic MASH progression. Treated then analyzed using both bulk single-cell RNA sequencing. Functional characterization was performed through staining BODIPY, TMRM, CellROX, Collagen I, as well terminal deoxynucleotidyl transferase dUTP nick end labeling ELISA assays. In addition, test validate hepatoprotective effects several herb extracts also conducted. Results: Both RNA-seq sequencing demonstrated close resemblance multiple signatures key intercellular communications in hepatocyte-like stellate-like model, compared Furthermore, functional revealed progressive features including severe steatosis, oxidative stress, mitochondrial dysfunction, inflammation, fibrosis. Schisandra antioxidative, anti-inflammatory, antifibrotic properties context Conclusions: This study offers an improved MASH, which can be potentially applied facilitate understanding pathogenesis discovery effective treatments.

Language: Английский

KLF7-regulated ITGA2 as a therapeutic target for inhibiting oral cancer stem cells DOI Creative Commons

Xin Qi,

Zhou Jiang, Pan Wang

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 2, 2025

Language: Английский

Citations

0
Integrated bulk and single-cell RNA sequencing unveils the temporal and spatial dynamics of epidermal cell adhesion DOI

Qingbo Zheng,

Pengjia Bao, Xiaoyun Wu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142601 - 142601

Published: March 1, 2025

Language: Английский

Citations

0
KLF7-Regulated ITGA2 as a Therapeutic Target for Inhibiting Oral Cancer Stem Cells DOI Open Access
Xin Qi, Zhou Jiang, Pan Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Cancer stem cells (CSCs) play crucial roles in tumor metastasis, therapy resistance, and immune evasion. Identifying understanding the factors that regulate stemness of presents promising opportunities for developing effective therapeutic strategies. In this study on oral squamous cell carcinoma (OSCC), we confirmed key role KLF7 maintaining OSCC. Using chromatin immunoprecipitation sequencing dual-luciferase assays, identified ITGA2, a membrane receptor, as downstream gene regulated by maintenance stemness. Tumor sphere formation flow cytometry analyses, vivo limiting dilution tumorigenicity evaluations demonstrated knocking down ITGA2 significantly impaired When bound to its ECM ligand, type I collagen, activates several stemness-related pathways, including PI3K-AKT, MAPK, Hippo. TC-I 15, which inhibits ITGA2–collagen interaction, showed synergistic anti-tumor effect when combined with cisplatin both vitro xenograft models. summary, reveal KLF7/ITGA2 axis is modulator Our findings suggest target, offering novel anti-CSC strategy. Highlights 1) molecule cancer 2) ITGA2as 3) interacts extracellular matrix activating pathways promoting YAP1 nuclear translocation sustain OCSCs. 4) providing new strategy overcome OSCC drug resistance.

Language: Английский

Citations

0
KLF7-Regulated ITGA2 as a Therapeutic Target for Inhibiting Oral Cancer Stem Cells DOI Creative Commons
Jiong Lyu, Xin Qi, Haoran Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Cancer stem cells (CSCs) play crucial roles in tumor metastasis, therapy resistance, and immune evasion. Identifying understanding the factors that regulate stemness of presents promising opportunities for developing effective therapeutic strategies. In this study on oral squamous cell carcinoma (OSCC), we confirmed key role KLF7 maintaining OSCC. Using chromatin immunoprecipitation sequencing dual-luciferase assays, identified ITGA2, a membrane receptor, as downstream gene regulated by maintenance stemness. Tumor sphere formation flow cytometry analyses, vivo limiting dilution tumorigenicity evaluations demonstrated knocking down ITGA2 significantly impaired When bound to its ECM ligand, type I collagen, activates several stemness-related pathways, including PI3K-AKT, MAPK, Hippo. TC-I 15, which inhibits ITGA2–collagen interaction, showed synergistic anti-tumor effect when combined with cisplatin both in vitro xenograft models. summary, reveal KLF7/ITGA2 axis is modulator Our findings suggest target, offering novel anti-CSC strategy.

Language: Английский

Citations

0
Modeling metabolic-associated steatohepatitis with human pluripotent stem cell-derived liver organoids DOI Creative Commons
Xiaoshan Wu, Dacheng Jiang, Yuchen Wang

et al.

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(12)

Published: Nov. 29, 2024

Background: Metabolic-associated steatohepatitis (MASH) is one of the most prevalent liver diseases worldwide, with a global prevalence estimated between 3% and 5%, posing significant health burden. Human organoids (HLOs) have previously been generated to model steatohepatitis, offering potential cellular disease for studying MASH. However, current HLO lacks detailed molecular characterizations requires further improvement. Methods: HLOs derived from human pluripotent stem cells were treated oleic acid TGFβ mimic MASH progression. Treated then analyzed using both bulk single-cell RNA sequencing. Functional characterization was performed through staining BODIPY, TMRM, CellROX, Collagen I, as well terminal deoxynucleotidyl transferase dUTP nick end labeling ELISA assays. In addition, test validate hepatoprotective effects several herb extracts also conducted. Results: Both RNA-seq sequencing demonstrated close resemblance multiple signatures key intercellular communications in hepatocyte-like stellate-like model, compared Furthermore, functional revealed progressive features including severe steatosis, oxidative stress, mitochondrial dysfunction, inflammation, fibrosis. Schisandra antioxidative, anti-inflammatory, antifibrotic properties context Conclusions: This study offers an improved MASH, which can be potentially applied facilitate understanding pathogenesis discovery effective treatments.

Language: Английский

Citations

0