Stimulation of rodent and human beta-cell proliferation using synthetic modified mRNAs encoding cell cycle regulators

Heterogeneity in cell-cycle dynamics of synthetic mRNA-induced β-cell proliferation

Pharmacologic HIF-2α inhibition preserves T cell effector function in clear cell renal cell carcinoma.

Hypoxia-inducible factor 2α (HIF-2α) is a central oncogenic driver in clear cell renal cell carcinoma (ccRCC) and a therapeutic target of the small-molecule inhibitor belzutifan. Genetic studies in murine models have suggested that hypoxia signaling may support T cell effector programs, raising concern that HIF-2α inhi...

CD98hc marks a precursor of human stem cell-derived alpha cells primed for functional maturation

Introduction Pluripotent stem cell-derived alpha cells (SC-α cells) represent a promising component of next-generation cell therapies designed to more fully recapitulate human islet function; however, heterogeneity and the presence of undesired side populations limit their functional maturity and therapeutic potential....

Comparison of cell-cycle gene expression dynamics and mRNA kinetics across mouse and human pluripotent systems

Cell-cycle remodeling is fundamental to pluripotency and lineage commitment, yet whether its transcriptional and post-transcriptional architecture is conserved across species and developmental states has remained unresolved. Here we introduce Ciclopes, a biology-informed deep-learning framework that resolves continuous...

Single-cell gene regulatory networks characterize colonic stem and immune cell homeostasis in Nr4a1 knockout mice

Summary Recent findings suggest that the orphan nuclear receptor 4A (NR4A) can regulate cellular energetics and epithelial defenses, contributing to a resilient, disease-resistant phenotype. To further examine the effects of NR4A on intestinal epithelial, stromal, and immune cell homeostasis, we performed single-cell t...

Mitochondrial ATP promotes T cell differentiation through chromatin accessibility.

Immune elimination of chronic infection or cancer requires cytotoxic CD8+ T cells that adopt and maintain an effector phenotype. Cytotoxic T cell function is a bioenergetically demanding process. Here, we report the ability of D-α-hydroxybutyrate (DAHB) to act as a signaling molecule that increases mitochondrial ATP pr...