Trends in Cell Biology最新文献

Lactate, a glycolytic intermediate, has a crucial role in cancer metabolism and microenvironment remodeling. Recently, researchers found that lactate mediates lysine lactylation, a novel protein post-translational modification (PTM). Here, we summarize the mechanism and role of lysine lactylation in cancer, and discuss the potential of targeting lysine lactylation in cancer therapy.

Endothelial cells (ENCs) and epithelial cells (EPCs) form monolayers whose barrier function is critical for the maintenance of physiological processes and extremely sensitive to mechanical cues. Computational models have emerged as powerful tools to elucidate how mechanical cues impact the behavior of these monolayers in health and disease. Herein, the importance of mechanics in regulating ENC and EPC monolayer behavior is established, highlighting similarities and differences in various biological contexts. Concurrently, computational approaches and their importance in accelerating mechanobiology studies are discussed, emphasizing their limitations and suggesting future directions. The aim is to inspire further synergies between cell biologists and modelers, which are crucial for accelerating cell mechanobiology research.

Mechanotransduction is the process by which cells detect mechanical forces and convert them into biochemical or electrical signals. This process occurs across various cellular compartments, including the plasma membrane, cytoskeleton, and intracellular organelles. While research has focused mainly on force sensing at the plasma membrane, the mechanisms and significance of intracellular mechanotransduction are just beginning to be understood. This review summarizes current techniques for studying organellar mechanobiology, and highlights advances in our understanding of the mechanosensitive events occurring in organelles such as the endoplasmic reticulum (ER), Golgi apparatus, and endolysosomes. Additionally, some open questions and promising directions are identified for future research.

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, and in vivo resemblance, current efforts are directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches and their latest developments are discussed, including stem cell optimization, refining morphogen administration strategies, altering the extracellular matrix (ECM) niche, and manipulating tissue architecture to mimic in vivo brain morphogenesis. Additionally, strategies to increase cell diversity and enhance organoid maturation, such as establishing co-cultures, assembloids, and organoid in vivo xenotransplantation, are reviewed. We explore how these various factors can be tuned and intermingled and speculate on future avenues towards even more physiologically-advanced brain organoids.

Lipids are major cell constituents endowed with astonishing structural diversity. The pathways responsible for the assembly and disposal of different lipid species are energetically demanding, and genes encoding lipid metabolic factors and lipid-related proteins comprise a sizable fraction of our coding genome. Despite the importance of lipids, the biological significance of lipid structural diversity remains largely obscure. Recent technological developments have enabled extensive lipid analysis at the single cell level, revealing unexpected cell-cell variability in lipid composition. This new evidence suggests that lipid diversity is exploited in multicellularity and that lipids have a role in the establishment and maintenance of cell identity. In this review, we highlight the emerging concepts and technologies in single cell lipid analysis and the implications of this research for future studies.

The generation of regulatory T cells (Tregs) through interactions with antigen-presenting cells (APCs) is essential for establishing tolerance to gut commensals. Recent findings highlight the critical role of RORγt-lineage APCs, especially in gut-associated lymphoid tissues, in the induction of microbiota-specific peripheral Tregs and maintaining gut immune homeostasis.

With advances in underlying technologies such as complex multicellular systems, synthetic materials, and bioengineering techniques, we can now generate in vitro miniaturized human tissues that recapitulate the organotypic features of normal or diseased tissues. Importantly, these 3D culture models have increasingly provided experimental access to diverse and complex tissues architectures and their morphogenic assembly in vitro. This review presents an analytical toolbox for biological researchers using 3D modeling technologies through which they can find a collation of currently available methods to phenotypically assess their 3D models in their normal state as well as their response to therapeutic or pathological agents.

Cell homeostasis and function rely on well-orchestrated communication between different organelles. This communication is ensured by signaling pathways and membrane contact sites between organelles. Many players involved in organelle crosstalk have been identified, predominantly proteins and ions. The role of lipids in interorganelle communication remains poorly understood. With the development and broader availability of methods to quantify lipids, as well as improved spatiotemporal resolution in detecting different lipid species, the contribution of lipids to organelle interactions starts to be evident. However, the specific roles of various lipid molecules in intracellular communication remain to be studied systematically. We summarize new insights in the interorganelle communication field from the perspective of organelles and discuss the roles played by lipids in these complex processes.

Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) function as transient signaling platforms that regulate essential cellular functions. MERCS are enriched in specific proteins and lipids that connect mitochondria and the ER together and modulate their activities. Dysregulation of MERCS is associated with several human pathologies including Alzheimer's disease (AD), Parkinson's disease (PD), and cancer. BCL-2 family proteins can locate at MERCS and control essential cellular functions such as calcium signaling and autophagy in addition to their role in mitochondrial apoptosis. Moreover, the BCL-2-mediated apoptotic machinery was recently found to trigger cGAS-STING pathway activation and a proinflammatory response, a recognized hallmark of these diseases that requires mitochondria-ER interplay. This review underscores the pivotal role of MERCS in regulating essential cellular functions, focusing on their crosstalk with BCL-2 family proteins, and discusses how their dysregulation is linked to disease.

The role of primary cilia has recently garnered significant attention in the field of neurodegeneration. This review explores the diversity of primary cilia in the mature brain and their interrelationships with a multitude of cellular structures, including axons and synapses. Importantly, an overview of the growing prominence of ciliary-related dysfunctions in neurodegenerative diseases is summarized, with a special emphasis on Parkinson's disease (PD) and neuropsychiatric disorders.