Trends in Cell Biology最新文献

Mitochondrial metabolism plays a central role in the regulation of hematopoietic stem cell (HSC) biology. Mitochondrial fatty acid oxidation (FAO) is pivotal in controlling HSC self-renewal and differentiation. Herein, we discuss recent evidence suggesting that NADPH generated in the mitochondria can influence the fate of HSCs. Although NADPH has multiple functions, HSCs show high levels of NADPH that are preferentially used for cholesterol biosynthesis. Endogenous cholesterol supports the biogenesis of extracellular vesicles (EVs), which are essential for maintaining HSC properties. We also highlight the significance of EVs in hematopoiesis through autocrine signaling. Elucidating the mitochondrial NADPH-cholesterol axis as part of the metabolic requirements of healthy HSCs will facilitate the development of new therapies for hematological disorders.

Aging is a dynamic process that is driven by cellular damage and disruption of homeostatic gene regulatory networks (GRNs). Traditional studies often focus on individual genes, but understanding their interplay is key to unraveling the mechanisms of aging. This review explores the gene circuits that influence longevity and highlights the role of feedback loops in maintaining cellular balance. The SIR2-HAP circuit in yeast serves as a model to explore how mutual inhibition between pathways influences aging trajectories and how engineering stable fixed points or oscillations within these circuits can extend lifespan. Feedback loops crucial for maintaining homeostasis are also reviewed, and we highlight how their destabilization accelerates aging. By leveraging systems and synthetic biology, strategies are proposed that may stabilize these loops within single cells, thereby enhancing their resilience to aging-related damage.

Studies of embryonic plasticity, which were foundational for developmental biology, revealed variation across species and patterns of association with cleavage programs and adult regenerative capacity. Modern molecular and genetic tools now enable a reexamination of these classical experiments in diverse species and have the potential to reveal mechanisms that regulate plasticity over developmental time. This review synthesizes previous work on plasticity in embryos and adults and associated genetic mechanisms, providing a framework to organize data from a wide range of species. Mechanisms that explain how plasticity is lost in mammalian embryos are highlighted and crystallize a proposal for future studies in new research organisms that could identify shared principles for embryonic plasticity and, potentially, its maintenance into adulthood.

Embryo growth, morphogenesis, and patterning are complex processes that coordinate between cellular dynamics, fate specification, and multiscale physical forces. Understanding how robustness in embryo development is achieved despite inherent heterogeneities in gene expression, cell properties, and tissue growth is a fundamental question. Although various feedback between gene expression, signaling, and cell and tissue mechanics have been uncovered to confer robustness on developmental systems, measuring variability and robustness from a quantitative perspective often remains challenging. Furthermore, cell fate plasticity, a key mechanism that can confer robustness, is lacking in many developing tissues. This review highlights how recent technological and conceptual advances in quantitative approaches to biology help to overcome these bottlenecks, with a particular focus on how mechanochemical feedback, or alternatively, selectively tuned control parameters, ensure developmental robustness.

The cell cycle is governed by tightly regulated checkpoints and proteogenomic oscillations that ensure genomic fidelity during cell proliferation. Dysregulation of the cell cycle can drive oncogenic transformation, and this positions it as a pivotal target in precision oncology. Recent advances reveal how proteomic and post-translational dynamics orchestrate cell-cycle phase transitions that are aberrantly disrupted in cancers. Therapeutic targeting of the CDK4/6 represents a cornerstone of cancer therapy, but resistance mechanisms limit its clinical efficacy. Emerging strategies such as targeted protein degradation, synthetic lethality, and combination immunotherapies further expand the therapeutic window. These innovations, coupled with biomarker-driven precision medicine, exploit cell-cycle vulnerabilities and transform them into an active tool to combat human cancers more effectively. This review highlights emerging mechanistic insights underlying tumorigenesis driven by an aberrant cell cycle and proposes potential therapeutics aimed at cell-cycle machinery-relevant targets.

Innate immune sensing through cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) surveils cytosolic DNA from invading pathogens or damaged organelles and initiates a spectrum of immune responses. It is well established that upon 2'3'-cyclic GMP-AMP (cGAMP) binding, STING exits the endoplasmic reticulum (ER), traverses the Golgi to trigger interferon programs, and finally reaches lysosomes for signal resolution through degradation, revealing a tightly choreographed itinerary for cytokine-driven immunity. However, emerging studies reveal additional layers of spatiotemporal complexity: ER-resident STING tunes in messenger RNA translation and Ca²⁺ efflux, Golgi-localized STING functions as a proton channel that initiates H⁺-dependent autophagy and transcription factor EB-directed programs for organelle homeostasis, and various mechanisms for metabolic remodeling and cell fate determination. This review synthesizes emerging organelle-specific mechanisms of cGAS-STING, delineates their roles in physiology and disease, and discusses how an organelle-centric perspective may inform selective, context-sensitive immunotherapies.

Lysosomes are essential membrane-bound organelles that control cellular homeostasis by integrating intracellular functions with external signals. Their critical roles make lysosomal membranes vulnerable to rupture under various stressors, leading to cellular dysfunction. However, the mechanisms by which cells respond to lysosomal damage have only recently begun to be explored. In this review, we summarize the cellular mechanisms activated by lysosomal damage, emphasizing those that restore lysosomal integrity and sustain homeostasis, including recognition, repair, removal, replacement, and remodeling. Drawing on our expertise, we provide an in-depth focus on the remodeling process involved in these responses, including metabolic signaling and stress granule formation. Finally, we discuss the implications of lysosomal damage in human diseases, underscoring potential therapeutic strategies to preserve lysosomal function and alleviate related disorders.

Latin America shows increasing scientific potential, with a dedicated and creative research community, driven by resilience and adaptability. However, limited funding, restricted access to cutting-edge technology, bureaucratic barriers, and constantly changing scientific policies continue to hinder its full integration into the international scientific ecosystem. Latin American scientists also suffer from limitations in their visibility on the global stage, often leading to exclusion. Despite these challenges, many success cases in the region highlight how strategic actions based on planned and sustained investments, international collaborations, and a relevant scientific policy positively impact scientific progress. Through this path, Latin America may not only overcome existing barriers but also position itself as a fundamental player in the scientific stage.

Despite its economic and population status, Mexico's scientific output remains under 1% of global production because of low spending on science. Yet, additional challenges, including over-reliance on expensive imported technology, brain drain, and limited private sector investment, further hinder its progress. Nonetheless, significant opportunities exist, such as fostering local biotechnology, enhancing policy continuity, and leveraging new leadership to boost scientific growth. Although focused on Mexico, these insights hold relevance for the broader region of Latin America, a region that shares vast untapped scientific potential.

Autophagy is a crucial 'self-eating' mechanism used by eukaryotic cells to degrade and recycle cytosolic materials. A recent study by Da Graça et al. reports that the dynamic mobilization of endosome-endoplasmic reticulum (ER) contact sites (EERCS) in response to starvation creates a confined environment that facilitates Ca²⁺-dependent phagophore biogenesis.