Trends in Cell Biology最新文献

Ever since BRCA1 germline mutations were found to confer a strong predisposition to the development of breast and ovarian cancers, there has been great interest in determining how this protein suppresses tumor formation. Through more than two decades of research, it has become clear that BRCA1 safeguards our genome mainly by promoting DNA repair through homologous recombination (HR). This opinion article outlines our evolving view of BRCA1's role in end resection, an upstream commitment step for HR, and highlights recent discoveries suggesting that the context in which DNA breaks are generated dictates whether BRCA1 is required for end resection. In addition, strong emerging evidence for the tumor-suppressive function of BRCA1 being mediated predominantly by its indispensable role in supporting RAD51-dependent recombination downstream of end resection is discussed.

Mitosis is a cellular process that demands high energy, but it was previously unclear how this process is linked with mitochondrial ATP production. Zhao et al. describe how during mitosis, the lamin B receptor migrates to the ER membrane to enhance ER-mitochondria contact sites, coordinating Ca²⁺ surges that increase ATP production necessary for cell division.

Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into longevity and potential therapeutic strategies. This review examines emerging mechanistic links between proteostasis and HSC fate, concluding with unresolved questions and challenges of the current research.

Genes burst. Instead of being monotonously transcribed by a steady stream of RNA polymerases, active genes undergo transient and random pulses of transcription that are referred to as gene bursting. This property is ubiquitous and evolutionarily conserved from bacteria to humans, and reflects the inherent stochastic nature of most biological processes. The frequency and duration of gene busting events varies greatly between genes and is now recognized to be controlled by an intricate interplay between transcription factors, chromatin features, and the transcription machinery. Recent findings also point to proximal regulation of bursting by epigenetic chromatin states, a novel role of non-histone modifications, and of distal control of bursting patterns by enhancers. Uncovering the regulatory mechanisms of gene bursting sheds light on how cells maintain a diverse range of gene-specific expression by modulating the different kinetic parameters of bursting.

The 3D folding of the genome is tightly linked to its epigenetic state which maintains gene expression programmes. Although the relationship between gene expression and genome organisation is highly context dependent, 3D genome organisation is emerging as a novel epigenetic layer to reinforce and stabilise transcriptional states. Whether regulatory information carried in genome folding could be transmitted through mitosis is an area of active investigation. In this review, we discuss the relationship between epigenetic state and nuclear organisation, as well as the interplay between transcriptional regulation and epigenetic genome folding. We also consider the architectural remodelling of nuclei as cells enter and exit mitosis, and evaluate the potential of the 3D genome to contribute to cellular memory.

Research into the crosstalk between α-synuclein (α-syn) and synaptic vesicles (SVs) has gained considerable attention. Notably, the recently discovered liquid-liquid phase separation of α-syn involving SVs is crucial for performing their physiological functions and mediating the transition to pathological aggregates. This review first examines the functional interactions between α-syn and SVs in the context of α-syn's condensation state. It then explores how these interactions become disrupted under pathological conditions, leading to α-syn aggregation and subsequent synaptic dysfunction. Finally, the review discusses the therapeutic potential of targeting α-syn-SV interactions to restore synaptic function in diseased states. By connecting α-syn's physiological roles with its pathological effects, the article aims to shed light on its dual role as both a regulator of SVs and a driver of neurodegeneration.

Mesenchymal stem cell (MSC) therapy shows great potential for treating tissue impairments and immune disorders. Epigenetic regulation is a core molecular signature that ensures long-lasting memory in MSC functional modulation and mediates therapeutic efficacy. Studies reveal that transplanted MSCs drive epigenetic changes in recipient cells, which contributes to restoration of organismal and microenvironmental homeostasis. Extracellular vesicles (EVs) derived from MSCs, including exosomes and apoptotic vesicles (apoVs), enable the transfer of epigenetic regulators, orchestrating intercellular epigenetic reprogramming and signaling modulation in both local and systemic microenvironments. Here, the epigenetic regulation of MSC and EV therapies is reviewed, together with current challenges, aiming to deepen the understanding of donor-recipient communication and inspire next-generation approaches to counteract tissue defects and diseases.

Metastasis, the dissemination of tumor cells from the primary site to distant organs, remains the leading cause of cancer-related mortality. This complex, multistep process demands not only cellular motility but also adaptation to diverse and often hostile microenvironments. Among key stressors, oxidative stress driven by elevated levels of reactive oxygen species (ROS) emerges as both a threat to survival and a modulator of metastatic traits. Tumor cells face oxidative pressure throughout the metastatic cascade, requiring mechanisms to mitigate ROS-induced damage while harnessing redox signaling to support progression. This review outlines how cancer cells respond to oxidative stress during metastatic spread, delineates stepwise roles of ROS across the cascade, and explores therapeutic strategies to disrupt redox dynamics in metastatic disease.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, muscle wasting, and eventual paralysis. The clinical and genetic complexity along with rapid disease progression has hindered efforts to model the disease and develop effective treatments. Rodent models and human tissue studies point to dysfunction in oligodendrocyte lineage cells early in disease, although the underlying mechanisms remain unclear. Advances in stem cell research have introduced novel platforms to investigate cells in the oligodendrocyte lineage and their interactions with neurons and other glial cells in complex human genetic backgrounds. This Review summarizes the literature implicating oligodendrocyte lineage cells in ALS and discusses both the potential and limitations of in vitro-derived cultures to shed light on their vulnerabilities and cellular interactions.

Chhikara et al. reframe stromal interaction molecule (STIM) proteins as structural organizers of membrane contact sites, not just calcium-entry activators, in neurons. STIM2 maintains resting endoplasmic reticulum (ER)-plasma membrane (PM) junctions; STIM1 dynamically expands them during neuronal activity. This activity-dependent remodeling tunes ER-PM proximity and calcium coupling, shifting focus from channel gating to spatial organization.