Genetic screens facilitate advances in biology, yet functional dissection of large mammalian proteins has remained challenging. A new study in Nature Communications by Corinne Kaufmann from the Wutz group (IMHS) uses targeted point mutagenesis of haploid cells to functionally map regulators at single amino acid resolution. Application of the method reveals critical amino acids of the silencing factor SPEN in X chromosome inactivation.
We demonstrate here that the abundance of polyunsaturated phospholipids (PUFAs) determines the sensitivity of T cells to ferroptosis, with effector T cells that are enriched in PUFAs being highly susceptible, in contrast to memory T cells that are resistant to ferroptosis due to a scarcity of PUFAs.
Haploid embryonic stem cells are powerful tools but tend to revert to a diploid state, limiting their use. Di Minin et al. show that this instability arises from a metabolic imbalance caused by altered cell size and mitochondrial density, leading to redox dysregulation. Correcting this imbalance stabilizes the haploid genome and links cellular metabolism to chromosome stability.
Eberhart et al. show that systemic peroxisome deficiency results in widespread hypomyelination throughout the central nervous system. This defect is linked to significant metabolic and signaling disruption.