Cold Spring Harbor perspectives in biology最新文献

Telomeric repeat-containing RNA (TERRA) molecules are transcripts comprising extended stretches of telomeric G-rich repeats, which are generated from telomeres or intrachromosomal loci. TERRA production is an evolutionarily conserved process observed across all eukaryotic kingdoms. While originally thought to localize and function only at telomeres, it is now clear that TERRA is involved in numerous cellular pathways beyond telomere maintenance, including gene expression regulation and signaling of dysfunctional telomeres to the cytoplasm and the extracellular environment. In this work, we will review key aspects of TERRA biogenesis, regulation, and functional relevance and propose models to reconcile the multiple and sometimes contradictory functions ascribed to TERRA. Based on TERRA interaction with proteins involved in disparate cellular processes, we also suggest that the full spectrum of TERRA-associated functions is still far from being completely unveiled. We anticipate that further study of this complex and fascinating RNA will reveal additional surprises in the future.

Cell migration in confined environments follows distinct mechanisms compared to conventional 2D migration. By using in vitro models and incorporating extracellular cues from the tissue microenvironment, we can gain deeper insights into the complexities of cell migration. In this work, we explore various engineered in vitro models to study cell migration. We delve into biophysical tools, such as traction force microscopy, to understand how cells generate forces in response to their surroundings. We highlight the use of novel optogenetic tools for precise, spatiotemporal control of protein expression at the cellular level. Lastly, we examine emerging therapeutic strategies designed to target abnormal cell migration.

The nervous system comprises a remarkably diverse and complex network of cell types, which must communicate with one another with speed, reliability, and precision. Thus, the developmental patterning and maintenance of these cell populations and their connections with one another pose a rather formidable task. Emerging data implicate microglia, the resident myeloid-derived cells of the central nervous system (CNS), in spatial patterning and synaptic wiring throughout the healthy, developing, and adult CNS. Importantly, new tools to specifically manipulate microglia function have revealed that these cellular functions translate, on a systems level, to effects on overall behavior. In this review, we give a historical perspective of work to identify microglia function in the healthy CNS, and highlight exciting new discoveries about their contributions to CNS development, maintenance, and plasticity.

Although cell migration has been extensively investigated using in vitro model systems, the mechanisms underlying mammalian cell migration in native tissue environments remain underexplored. Moreover, efforts to directly manipulate and visualize molecular regulators in live mammalian tissues have been scarce. In this article, we first review the current insights into various single-cell migration phenomena, including stem cell types, observed in mammalian tissues under homeostatic and pathophysiological conditions. Thereafter, we discuss intravital subcellular microscopy (ISMic) as a tool to unravel membrane remodeling mechanisms underlying cell migration in live animal tissues. Lastly, we emphasize the need for innovative microscopy and complementary advanced approaches to achieve a deeper fundamental understanding of cell migration modalities and their impact on mammalian tissue in homeostasis and pathophysiology.

trans-Translation is a recoding event in which a translating ribosome switches from the engaged messenger RNA (mRNA) to a specialized reading frame within transfer-messenger RNA (tmRNA) without releasing the nascent polypeptide, producing a protein that is encoded in two physically distinct RNA molecules. trans-Translation is the most abundant form of recoding and is found throughout the bacterial kingdom. In Escherichia coli growing in liquid culture, ∼5% of newly synthesized proteins are recoded through trans-translation. The importance of this pathway for pathogenic bacteria makes it a potential target for antibiotic development. This review covers the role of trans-translation in pathogenesis, potential points for inhibition, and the progress in developing trans-translation inhibitors as antibiotics.

Cell migration is greatly affected by both the physical properties of the motile cell itself and the environment through which the cell is moving. In addition to studying cellular and extracellular mechanical properties in the context of cell migration, there is a growing interest in understanding the intersection between migration, mechanics, and metabolism. In this work, we discuss the many techniques and approaches researchers are currently using to study cellular mechanics, extracellular mechanics, and metabolism in the context of cell migration. Our goal is to bring exposure to new approaches in the fields of mechanobiology and mechanometabolism and highlight the importance of studying cell migration through a mechanical lens.

This perspective advocates for "evolutionary systems neuroscience" as a framework combining evolutionary biology with neural circuit analysis. Evolution creates natural circuit modifications that preserve essential functions while enabling new behaviors. Modern technologies now allow researchers to investigate causal connections from genes to circuits to behaviors with unprecedented precision. By studying both convergent and divergent evolution, we can uncover both broad computational principles and specific implementation mechanisms. Across diverse examples-from insect courtship to rodent communication-we explore how targeted circuit changes drive behavioral innovation without disrupting core functions. This framework may reveal "deep homologies" in neural mechanisms, similar to how evolutionary developmental biology (evo-devo) identified conserved genetic toolkits in morphological development. This evolutionary lens promises not just to reveal how brains work, but why they work the way they do-providing insights that extend beyond neuroscience to complex adaptive systems more broadly.

Cell migration is a fundamental biological process critical for development, immune response, and wound healing, but its dysregulation contributes to pathological conditions such as cancer metastasis. Recent research has demonstrated that migration is driven by excitable signal transduction and cytoskeletal networks, which function as separate but coupled systems. The signal transduction excitable network (STEN) propagates excitatory signals, while the cytoskeletal excitable network (CEN) generates cytoskeletal protrusions. Although distinct, these networks interact dynamically: STEN regulates CEN, while CEN provides feedback to STEN, influencing cell polarization and directionality. Computational models incorporating nonlinear dynamics and reaction-diffusion systems have successfully recapitulated these interactions, shedding light on their role in pseudopod formation, chemotaxis, and mechanosensation. This review discusses recent experimental and theoretical advances, highlighting how excitable systems underlie cell motility and how mathematical modeling helps to understand their role.

Directed leukocyte motility is essential for immunity and host defense. Dysregulated leukocyte migration is implicated in clinical immunodeficiency and hyperinflammatory conditions. Leukocytes sense both chemical and physical cues within the environment to regulate internal migration machinery and thus coordinate the immune response and its resolution. In response to environmental cues, leukocytes cater migration strategies to both exert forces on surrounding tissues and alter the chemical environment through self-generated gradients. Here, we synthesize recent advances in our understanding of how chemical and physical cues within the tissue environment regulate leukocyte motility, with implications to develop therapeutic strategies to modulate the immune response in human disease.

During development and homeostasis, tissues move and rearrange to form organs, seal wounds, or-in the case of cancer-spread in the body. To accomplish this, cells in tissues need to communicate with each other, generate force to push themselves forward, and know where to go to-all of this with little to no error. Here, we discuss how a migrating tissue-the zebrafish posterior lateral line primordium-solves these challenges. We focus on the strategies that ensure signaling within the tissue, enable the tissue to generate and transmit force to its substrate for propulsion, and allow robust directional sensing and migration by the tissue. These strategies include facilitated diffusion and ligand trapping for focal signaling, a self-generated attractant gradient for long-distance migration, clamping of the attractant concentration to the attractant receptor's K _d for most sensitive signaling, mechanical coupling among cells for averaging directional sensing in a tissue, and large rear traction stresses to propel the tissue forward. Many of these strategies likely apply to collectively migrating cells in other contexts and should thus provide insights with direct relevance to human health.