Nature Reviews Molecular Cell Biology最新文献

The generation of highly accurate models of behaviours of individual cells and cell populations through integration of high-resolution assays with advanced computational tools would transform precision medicine. Recent breakthroughs in single-cell and spatial transcriptomics and multi-omics technologies, coupled with artificial intelligence, are driving rapid progress in model development. Complementing the advances in artificial intelligence, quantum computing is maturing as a novel compute paradigm that may offer potential solutions to overcome the computational bottlenecks inherent to capturing cellular dynamics. In this Roadmap article, we discuss the advancements and challenges in spatiotemporal single-cell analysis, explore the possibility of quantum computing to address the challenges and present a case study on how quantum computing may be integrated into cell-based therapeutics. The specific confluence of quantum and classical computing with high-resolution assays may offer a crucial path towards the generation of transformative models of cellular behaviours and perturbation responses.

Cohesin is a key regulator of three-dimensional genome organization, contributing to gene regulation, recombination, DNA repair and chromosome segregation. Like other members of the evolutionary conserved structural maintenance of chromosomes (SMC) protein-complex family, cohesin folds DNA through motor-driven loop extrusion. Cohesin has a unique, second activity of genome organization: it physically links sister chromatids together in replicated chromosomes, a process termed sister chromatid cohesion. Sister chromatid cohesion and loop extrusion are mediated by two distinct pools of cohesin, which share common core subunits, but associate with distinct regulatory subunits to interact with chromosomes in fundamentally different ways. In this Review, we discuss how sister chromatid cohesion is established and regulated, and how an interplay between cohesion and chromatin loops organizes replicated chromosomes. We also discuss how cohesion supports chromosome segregation in mitosis and meiosis, and how it contributes to DNA double-strand break repair and age-related oocyte aneuploidy. We outline recent technological advances that provide new opportunities to study cohesion and the conformation of replicated chromosomes, and we provide a perspective on how these tools might be applied to answer fundamental questions in cohesin biology.

Extracellular vesicles (EVs) have gained significant attention owing to their role in pathophysiological processes and potential as therapeutic tools. EVs are small vesicles (30 nm-5 µm) containing specific cargo (proteins, nucleic acids and lipids) and are released from most cell types. Their capacity to target and induce phenotypical changes in recipient cells has established them as key mediators of intercellular communication. Although EV biogenesis is well studied, their uptake and fate in recipient cells are still poorly understood. In this Review, we focus on the cell biology underlying EV interactions with recipient cells and their intracellular fate. We discuss the mechanisms EVs use to achieve cell-specific targeting, cell signalling and functional cargo delivery and list the key challenges currently limiting our ability to harness these EVs into efficient therapeutic nanovehicles. We explore how our understanding of the molecular mechanisms supporting interactions of EVs with recipient cells and their functions herein can provide new strategies to use them for therapeutic approaches.