Annual review of cell and developmental biology最新文献

Stem cells are undifferentiated cells capable of self-renewal and differentiation into specialized cell types, forming the foundation of tissue maintenance and repair. In the blood system, this process is known as hematopoiesis. Hematopoietic stem cells (HSCs), positioned at the apex of the hematopoietic hierarchy, have the unique ability to reconstitute the hematopoietic system long-term. HSC stemness is defined by multipotency, allowing differentiation into all blood lineages, and self-renewal, maintaining the stem cell pool. A fundamental property of HSCs is quiescence, which refers to a reversible inactive cell cycle state that preserves their self-renewal potential. Dormant HSCs represent a subset of quiescent stem cells with minimal division rates and the most potent stemness. Dysregulation of dormancy and quiescence is linked to HSC dysfunction. Here, we explore mechanisms regulating HSC dormancy and quiescence under homeostatic and stress conditions. Finally, we describe how factors such as aging, inflammation, and malignancies disrupt these states.

Plants are subject to assault from numerous pathogens that colonize different tissues and organs that vary greatly in structure, nutrient availability, water status, and responsiveness to pathogens. Past research has focused on how plant immune receptors sense danger signals during infection and signaling mechanisms. How pathogens, particularly those that infect flowers and roots, breach physical barriers of different host tissues and establish niches for proliferation has received less attention. Recent advances indicate that different pathogens employ specialized mechanisms to manipulate the physiology, metabolism, growth, and development of specific host cells to breach various physical barriers and create a microenvironment suitable for pathogen proliferation and dissemination. Importantly, the plant immune system actively engages these processes to counter pathogenesis. Furthermore, emerging evidence increasingly points to different roles of specific plant cells in sensing the pathogen and cell-cell communication that is important for the establishment of immunity at the organism level.

Immune cells possess a remarkable set of complementary surface protrusions, such as microvilli, podosomes, filopodia, and lamellipodia, which play pivotal roles in the sensing of and responding to varied environmental cues. These dynamic structures maximize the surface area-to-volume ratio of immune cells, which in turn enhances cell-cell and cell-matrix interactions, while generating pulling and pushing forces, allowing immune cells to integrate biochemical and physical cues from their surroundings. This review discusses recent insights into the structures and dynamics of different protrusions, the molecular machinery behind mechanosensing, the differential role of protrusions for different subsets of immune cells, and the cutting-edge technology that has advanced our understanding of those protrusions.

The packaging and export of messenger RNA (mRNA) are essential cellular pathways that bridge the nuclear and cytoplasmic phases of eukaryotic gene expression. During their nuclear maturation, mRNAs are packaged by proteins into mRNA ribonucleoproteins (mRNPs). Other proteins then assist in the export of mRNPs into the cytoplasm for translation. Together, these proteins play critical roles in compacting the mRNA, defining mRNA identity, preventing unwanted interactions, and orchestrating mRNA transport through the nuclear pore complex (NPC). Here, we review decades of genetics and biochemistry alongside recent structural and functional insights and outline a general framework for the late stages of nuclear mRNA biogenesis and export. We also highlight open questions, including the mechanisms of mRNP packaging, mRNP export through the NPC, and the regulation, quality control, and exploitation of the pathway.

Nodal signaling molecules are TGFβ family ligands that arose early during bilaterian evolution and are crucial for several key steps in embryonic development. They regulate the specification of mesoderm and endoderm, body patterning, left-right asymmetry, and pluripotency maintenance. Many of Nodal's effects are tissue specific and achieved through interaction with other signaling pathways. Nodal has become a paradigm for a morphogen that employs multiple mechanisms for tissue patterning, including concentration- and duration-dependent effects, feedback regulation, reaction-diffusion interactions, and scale invariance. Nodal signaling activates a broad set of target genes that specify cell types, remodel the intracellular and extracellular milieu, and drive cell movements and morphogenesis. While Nodal's developmental functions are largely conserved across vertebrates, many facets of the mechanisms that elicit transcriptional responses and pattern embryonic tissues remain to be clarified.

Gene clusters generate proteome diversity required for cell fate and function. Given their genomic organization, wherein tandemly arranged genes with nearly identical promoter sequences neighbor shared enhancers, gene clusters present extreme cases of enhancer-promoter specificity, long-range enhancer-promoter communication, and chromatin compartmentalization. Here, we review recent advances in the regulation of protocadherin (Pcdh) and olfactory receptor (OR) gene clusters. These clusters present similar challenges in that cells must express a limited number of each type of gene stochastically. Probabilistic Pcdh and OR choice is accomplished through tunable enhancer-promoter interactions, but these interactions are regulated by distinct mechanisms. At the Pcdh locus, cohesin-mediated DNA loop extrusion dictates enhancer-promoter communication, whereas OR genes communicate with their enhancers through multichromosome assemblies involving the protein LDB1. In reviewing principles of Pcdh and OR regulation, we propose that gene clusters offer valuable paradigms for deciphering principles of gene expression regulation, with broad mechanistic and physiological implications for mammalian genome folding.

The neural crest is a highly migratory multipotent cell population traveling large distances in the vertebrate embryo. Neural crest cells migrate collectively in subpopulations, ranging in size from streams with hundreds of cells delaminating in the cephalic region to chains of single cells that delaminate in a dripping manner in the trunk. Here, we review the guidance mechanisms involved in neural crest migration and stream formation. We first describe established concepts of neural crest chemosensing and then highlight novel insights into biomechanical guidance. Finally, we propose how chemical and mechanical cues might interact and how neural crest cells can self-generate guidance gradients, facilitating robust guidance. Through this, we describe the mechanisms enabling neural crest cells to swarm collectively over large distances in a coordinated and directional manner within the complex in vivo environment of an embryo.

Biomolecular condensates provide a way to compartmentalize subcellular components with high temporal and spatial resolution, enabling rapid responses to signals and environmental changes. While the formation, components, and function of some condensates are well-characterized, their presence across organisms, their evolutionary history, and their origin are less well-understood. Here, we review the diversity of condensate components and highlight that not only disordered but also fully structured proteins are capable of driving condensate formation. We compare how proteomes of condensates overlap within and across species, and we present functionally analogous condensates across organisms. Additionally, we discuss the potential role of condensation in early life, suggesting that phase separation could have facilitated the selection and concentration of prebiotic molecules, promoting essential biochemical processes. We conclude that condensate-related organization principles are ubiquitously used across organisms from bacteria to mammals, and they potentially played a key role in prebiotic evolution, serving as primitive compartments for early biochemical processes.

Aging is a universal biological phenomenon that affects all biological systems. It is characterized by the inability to remain in a balanced physiological state, leading to a functional decline of the organism and, in metazoa, an increased risk of age-related diseases. Identifying causal drivers of aging is a major challenge at the cellular level, but in the model organism Saccharomyces cerevisiae, recent technical advances enabling the full observation of its replicative lifespan have revealed a heterogeneous aging process characterized by unique temporal and functional dependencies between cellular subprocesses. Specifically, cellular aging progresses through different trajectories, representing successive stages of homeostatic loss throughout the organism's life. In this perspective, we review the latest cellular principles as learned from S. cerevisiae that are providing a better understanding of how cellular aging progresses in metazoa.

The RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) has recently emerged from relative obscurity to be recognized as a key player in a variety of inflammatory diseases, including cancer. This growing recognition has generated interest in developing ADAR1 inhibitors; however, several fundamental questions about the enzyme need to be answered before ADAR1-based therapies can be successful. In this review, we summarize the current understanding of ADAR1, including its protein structure, RNA substrates, and roles in both innate and adaptive immunity. Recent studies have shed light on ADAR1 protein interactions and its RNA editing-independent functions. We also explore the involvement of ADAR1 in human diseases, with a focus on its roles in various cancers. Drosophila lacks an ADAR1 homolog; instead, the ADAR2 homolog is responsible for editing double-stranded RNA to prevent aberrant activation of the innate immune system. Finally, we address major questions in the field that still remain unanswered.