Volume 25 Issue 3, March 2023

A study using a multi-organoid platform and state-of-the-art transcriptional profiling identifies potential therapeutic targets against SARS-CoV-2. The authors find that CIART, a gene involved in circadian regulation, promotes SARS-CoV-2 infection by regulating the retinoid X receptor pathway and fatty acid synthesis.

Programmed cell death (PCD) enables cells to co-ordinate their exit to benefit the surviving organism. A new study describes how cells can programme their death by inducing extensive disulfide bonding of the actin cytoskeleton in response to an imbalance of cystine, a raw material for glutathione production.

Extracellular matrix (ECM) stiffening is a hallmark of cancer aggressiveness. Diverse ECM environments can alter the number and cargo of small extracellular vesicles (sEVs). Wu et al. now delineate a pathway from ECM stiffness to FAK/PI3K/Akt signalling and Rab8-induced sEV secretion, promoting cancer growth.

Activation of a crucial immune adaptor protein, STING, is tightly regulated by subcellular trafficking, but how it is deactivated remains less well defined. A study now shows that ESCRT-dependent encapsulation of STING-carrying vesicles by lysosomal compartments — through the process of microautophagy — mediates the termination of STING signalling.

Systematic infection of a human multi-organoid system shows that deficiency in the host factor CIART impairs SARS-CoV-2 infection through downregulation of the RXR pathway and subsequent impairment of fatty-acid synthesis.

Huebner et al. develop a 2D culture system to study gastric isthmus stem cells and identify a role for Sox2 in specifying enterochromaffin cells in the stomach.

Liu, Nie et al. identify disulfidptosis as a form of cell death resulting from aberrant accumulation of disulfide bonds in actin cytoskeleton proteins that is induced following glucose starvation and dependent on SLC7A11-mediated cystine uptake.

Wu et al. report that a stiff extracellular matrix stimulates the release of exosomes from cancer cells under the control of Akt and Rab8. These exosomes in turn promote tumour growth.

Zanin, Viaris de Lesegno et al. identify what controls the endosomal activation of the IFNAR receptor by IFN-α and establish a central role for endosomal sorting via STAM and Hrs in the differential regulation of JAK–STAT signalling by IFN-α and IFN-β.

Harasimov et al. show that, in human and porcine oocytes, actin cables and microtubule loops move chromosomes into a cluster before spindle assembly to ensure fast and complete chromosome capture in meiosis.

Kuchitsu et al. show that STING-positive vesicles of a recycling endosome origin are encapsulated into lysosomes after STING ubiquitination and this process requires ESCRT proteins Tsg101 and Vps4.

Adriaenssens et al. provide evidence suggesting that cytosolic small heat shock proteins localize to the mitochondrial intermembrane space, where they operate as molecular chaperones.

Wong et al. report that expanding human embryonic stem cell-derived endodermal progenitors serve as a ventral foregut model, through which they identify a link between progenitor expansion and tissue-specific changes in the enhancer landscape.

Zou et al. show that SMARCD3 regulates DAB1 activity and Reelin signalling in the developing cerebellum, which can be hijacked to promote medulloblastoma cell migration and metastatic dissemination.