Volume 24 Issue 12, December 2022

For the past 40 years, minimal reconstituted systems have helped cell biologists to understand the mechanisms that underlie membrane traffic. Having progressed from minimal synthetic and cell-derived ensembles to direct comparison with living systems, reconstitution is poised for ever more precise and informative understanding of membrane biology.

The onset of differentiation has been assumed to follow withdrawal from the cell cycle. A new study shows that keratinocytes initiate differentiation before exiting the cell cycle, allowing the skin to respond rapidly to damage.

IL-2 is a powerful growth factor for T cells. New work shows that immune checkpoint blockade depends upon the presence of IL-2, and that mesenchymal stem cells can be efficiently engineered to safely deliver it directly in advanced tumours to rescue CD8⁺ T cell responsiveness to anti-PD-L1 antibody treatment.

Cockburn et al. report that epidermal differentiation is a multi-day process through which cells undergo a continuum of transcriptional alterations initiated independently of cell cycle exit.

Allen et al. identify a pathogenic role for microbial small RNAs enriched on low-density lipoprotein to activate TLR8 signalling, thereby promoting polarization of inflammatory macrophages and facilitating the development of atherosclerosis.

Efstathiou et al. describe an Argonaute-dependent endoplasmic reticulum (ER)-associated RNA silencing pathway that acts together with ER-associated protein degradation to preserve ER homeostasis and function.

Zhang et al. have data suggesting that, in the chicken embryo, monocytes foster a pro-angiogenic microenvironment in advance of angiogenesis by depositing migrasomes enriched in angiogenic factors.

Kwak et al. report that adherens junctions organize membrane microdomains, leading to lipid-dependent γ-secretase recruitment and size-dependent protein segregation, excluding full-length Notch receptor.

Bae et al. engineer mesenchymal stem cells to express and deliver IL-2 to tumour-infiltrating lymphocytes, leading to activation and expansion of CD8⁺ T cells and improved tumour control, overcoming adaptive resistance to immune checkpoint blockade.

Lim et al. developed a fluorescence resonance energy transfer-based assay to identify anti-CRISPR molecules and discovered an SpCas9 inhibitor that is twofold more efficient in inhibiting Cas9 at diverse genomic loci than existing inhibitors and easy to synthesize.