Zhou, Wang et al. show that induced polyploidy acts as an intrinsic cellular stress that reprograms epithelial cells to promote motility and phagocytic behavior. Through ER stress and ROS–JNK signaling, polyploid cells gain immune-like behaviors in development and cancer, linking increased genome content to invasive and metastatic traits.

Chen et al. establish a rosette-forming intermediate stem cell model that captures the peri-implantation transition. It reveals a bistable regulatory circuit where OTX2/ID1 synergy maintains pluripotency plasticity under MEK inhibition, thereby bridging a key gap in modeling the progression from naïve to formative states.

This study identifies a stress-responsive axis composed of HSF2 and HSP110 that preserves genome stability after x-irradiation. By safeguarding RNA polymerase II activity and the transcriptional output of DNA repair genes, this axis prevents replication stress and subsequent lymphoma development, highlighting a potential molecular target for clinical radiosensitization.

Krahn et al. use budding yeast to examine membrane recycling at the Golgi apparatus. They describe an in vivo vesicle capture assay that reveals which resident Golgi proteins recycle together in the same vesicles. The results point to a second COPI-dependent intra-Golgi recycling pathway that operates downstream of the previously described COPI-dependent pathway.

Vinayagamurthy et al. reveal TRF2 is integral for NSC identity. Surprisingly, non-telomeric function of TRF2, instead of commonly understood telomere protection by TRF2, is critical for NSCs. Direct association of TRF2 with DNA G-quadruplex motifs in promoters of differentiation-associated genes tightly regulates transcription to suppress neurogenesis.

Wang et al. show that migrasome formation requires tetraspanin 4 palmitoylation regulated by DHHC6 and PPT1. This modification drives tetraspanin 4 clustering with cholesterol to build migrasomes. A palmitoylation-deficient tetraspanin 4 mutant (6CA) acts as a dominant-negative tool, blocking migrasome formation and causing developmental defects in zebrafish embryos, establishing palmitoylation as a key regulator of this process.

Newly synthesized cholesterol is transported from the endoplasmic reticulum to the plasma membrane via specialized COPII-independent vesicles. This process requires ceramide for vesicle formation, caveolin proteins as the vesicle coat, and actin-based motors for delivery, revealing a major cellular pathway for cholesterol distribution.