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Rubio-Navarro et al. identify a subset of pancreatic beta cells marked by high CD63 levels with enhanced glucose-stimulated insulin secretion. CD63-high beta cells are diminished in mouse models of and in humans with type 2 diabetes.
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.
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.
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.
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.
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.
We discovered that SARS-CoV-2 infection causes DNA damage both in cultured cells and in vivo. Mechanistically, SARS-CoV-2 degrades the enzyme CHK1, which leads to a reduction in dNTPs and impaired DNA replication. Moreover, inhibition of the formation of binding protein 53BP1 foci by the SARS-CoV-2 nucleocapsid protein hinders the repair of damaged DNA. The ensuing accumulation of DNA damage causes cellular senescence and inflammation.
Gioia, Tavella et al. show that severe acute respiratory syndrome coronavirus 2 causes DNA damage through CHK1 degradation and impairs 53BP1 recruitment to DNA lesions. The induced DNA damage is associated with expression of pro-inflammatory cytokines and senescence markers.
Dimple Notani is principal investigator (PI) at the National Centre for Biological Sciences (NCBS) in Bangalore, India, studying gene regulation. Nature Cell Biology contacted Dimple to discuss the state of the field and her experience running a research lab in India through a pandemic and as a junior PI.
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.
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.
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.
Since stem cells were first discovered, researchers have identified distinct stem cell populations in different organs and with various functions, converging on the unique abilities of self-renewal and differentiation toward diverse cell types. These abilities make stem cells an incredibly promising tool in therapeutics and have turned stem cell biology into a fast-evolving field. Here, stem cell biologists express their view on the most striking advances and current challenges in their field.