Li, X. B. | bioRxiv Science

bioRxiv2024

Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (hiPSC) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity of differentiation into specific lineage. Characterization of the transcriptome of eleven hiPSC lines showed that activation of MIXL1 at the early stage of stem cell differentiation correlated with higher efficacy in generating definitive endoderm and advancing differentiation and maturation of endoderm derivatives. Enforced expression of MIXL1 in the endoderm-inefficient hiPSCs enhanced the propensity of endoderm differentiation, suggesting that modulation of key drivers of lineage differentiation can re-wire hiPSC to the desired lineage propensity to generate the requisite stem cell products.

developmental biology↗

bioRxiv2023

Tumor-derived exosomal miR-222-3p induce cancer-associated fibroblasts activation to foster progression of renal cancer

The interaction between tumor-derived exosomes and stroma is crucial for tumor progression. However, the mechanisms by which tumor cells influence stromal changes are not yet fully understood. Our study revealed that high-metastatic renal cancer cells are more effective in converting normal fibroblasts into cancer-associated fibroblasts (CAFs) compared to low-metastatic renal cancer cells. Meanwhile, high-metastatic renal cancer cells secrete more exosomal miR-222-3p, which can directly target PANK3, activate NF-kB signaling pathway in fibroblasts and induce intracellular metabolic reprogramming to produce more lactic acid through Warburg effect. The activated CAFs further promote renal cancer progression by secreting lactic acid and inflammatory cytokines, including IL-6 and IL-8. Patients with renal cancer who have high levels of serum exocrine miR-222-3p are more likely to experience progression. These findings suggest that the intercellular communication between renal cancer cells and fibroblasts is facilitated by tumor exosomes. Targeting this communication may hold promise for the prevention and treatment of renal cancer.

cancer biology↗