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The role of the haematopoietic stem cell niche in development and ageing 造血干细胞龛在发育和衰老中的作用
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-09-10 DOI: 10.1038/s41580-024-00770-8
Terri L. Cain, Marta Derecka, Shannon McKinney-Freeman
{"title":"The role of the haematopoietic stem cell niche in development and ageing","authors":"Terri L. Cain, Marta Derecka, Shannon McKinney-Freeman","doi":"10.1038/s41580-024-00770-8","DOIUrl":"https://doi.org/10.1038/s41580-024-00770-8","url":null,"abstract":"<p>Blood production depends on rare haematopoietic stem cells (HSCs) and haematopoietic stem and progenitor cells (HSPCs) that ultimately take up residence in the bone marrow during development. HSPCs and HSCs are subject to extrinsic regulation by the bone marrow microenvironment, or niche. Studying the interactions between HSCs and their niche is critical for improving ex vivo culturing conditions and genetic manipulation of HSCs, which is pivotal for improving autologous HSC therapies and transplantations. Additionally, understanding how the complex molecular network in the bone marrow is altered during ageing is paramount for developing novel therapeutics for ageing-related haematopoietic disorders. HSCs are unique amongst stem and progenitor cell pools in that they engage with multiple physically distinct niches during their ontogeny. HSCs are specified from haemogenic endothelium in the aorta, migrate to the fetal liver and, ultimately, colonize their final niche in the bone marrow. Recent studies employing single-cell transcriptomics and microscopy have identified novel cellular interactions that govern HSC specification and engagement with their niches throughout ontogeny. New lineage-tracing models and microscopy tools have raised questions about the numbers of HSCs specified, as well as the functional consequences of HSCs interacting with each developmental niche. Advances have also been made in understanding how these niches are modified and perturbed during ageing, and the role of these altered interactions in haematopoietic diseases. In this Review, we discuss these new findings and highlight the questions that remain to be explored.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanisms of mechanotransduction and physiological roles of PIEZO channels PIEZO 通道的机械传导机制和生理作用
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-09-09 DOI: 10.1038/s41580-024-00773-5
Bailong Xiao
{"title":"Mechanisms of mechanotransduction and physiological roles of PIEZO channels","authors":"Bailong Xiao","doi":"10.1038/s41580-024-00773-5","DOIUrl":"https://doi.org/10.1038/s41580-024-00773-5","url":null,"abstract":"<p>Mechanical force is an essential physical element that contributes to the formation and function of life. The discovery of the evolutionarily conserved PIEZO family, including PIEZO1 and PIEZO2 in mammals, as bona fide mechanically activated cation channels has transformed our understanding of how mechanical forces are sensed and transduced into biological activities. In this Review, I discuss recent structure–function studies that have illustrated how PIEZO1 and PIEZO2 adopt their unique structural design and curvature-based gating dynamics, enabling their function as dedicated mechanotransduction channels with high mechanosensitivity and selective cation conductivity. I also discuss our current understanding of the physiological and pathophysiological roles mediated by PIEZO channels, including PIEZO1-dependent regulation of development and functional homeostasis and PIEZO2-dominated mechanosensation of touch, tactile pain, proprioception and interoception of mechanical states of internal organs. Despite the remarkable progress in PIEZO research, this Review also highlights outstanding questions in the field.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamics of DNA replication speeds in single cells 单细胞中 DNA 复制速度的动态变化
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-09-05 DOI: 10.1038/s41580-024-00776-2
Jeroen van den Berg
{"title":"Dynamics of DNA replication speeds in single cells","authors":"Jeroen van den Berg","doi":"10.1038/s41580-024-00776-2","DOIUrl":"https://doi.org/10.1038/s41580-024-00776-2","url":null,"abstract":"In this Tools of the Trade article, Jeroen van den Berg (van Oudenaarden lab) presents a new method based on pulse-labelling of nascent DNA to study the dynamics of DNA replication in single cells.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CLASPing and squeezing during cell migration 细胞迁移过程中的 CLASPing 和挤压
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-09-04 DOI: 10.1038/s41580-024-00779-z
Lisa Heinke
{"title":"CLASPing and squeezing during cell migration","authors":"Lisa Heinke","doi":"10.1038/s41580-024-00779-z","DOIUrl":"https://doi.org/10.1038/s41580-024-00779-z","url":null,"abstract":"This study finds that microtubules act as a mechanostat during cell migration, becoming mechanically reinforced in response to compression to protect the nucleus and coordinate contractility.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanisms of assembly and remodelling of the extracellular matrix 细胞外基质的组装和重塑机制
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-09-02 DOI: 10.1038/s41580-024-00767-3
Alexandra Naba
{"title":"Mechanisms of assembly and remodelling of the extracellular matrix","authors":"Alexandra Naba","doi":"10.1038/s41580-024-00767-3","DOIUrl":"https://doi.org/10.1038/s41580-024-00767-3","url":null,"abstract":"<p>The extracellular matrix (ECM) is the complex meshwork of proteins and glycans that forms the scaffold that surrounds and supports cells. It exerts key roles in all aspects of metazoan physiology, from conferring physical and mechanical properties on tissues and organs to modulating cellular processes such as proliferation, differentiation and migration. Understanding the mechanisms that orchestrate the assembly of the ECM scaffold is thus crucial to understand ECM functions in health and disease. This Review discusses novel insights into the compositional diversity of matrisome components and the mechanisms that lead to tissue-specific assemblies and architectures tailored to support specific functions. The Review then highlights recently discovered mechanisms, including post-translational modifications and metabolic pathways such as amino acid availability and the circadian clock, that modulate ECM secretion, assembly and remodelling in homeostasis and human diseases. Last, the Review explores the potential of ‘matritherapies’, that is, strategies to normalize ECM composition and architecture to achieve a therapeutic benefit.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epigenetic gene regulation in plants and its potential applications in crop improvement. 植物表观遗传基因调控及其在作物改良中的潜在应用。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-08-27 DOI: 10.1038/s41580-024-00769-1
Heng Zhang, Jian-Kang Zhu
{"title":"Epigenetic gene regulation in plants and its potential applications in crop improvement.","authors":"Heng Zhang, Jian-Kang Zhu","doi":"10.1038/s41580-024-00769-1","DOIUrl":"https://doi.org/10.1038/s41580-024-00769-1","url":null,"abstract":"<p><p>DNA methylation, also known as 5-methylcytosine, is an epigenetic modification that has crucial functions in plant growth, development and adaptation. The cellular DNA methylation level is tightly regulated by the combined action of DNA methyltransferases and demethylases. Protein complexes involved in the targeting and interpretation of DNA methylation have been identified, revealing intriguing roles of methyl-DNA binding proteins and molecular chaperones. Structural studies and in vitro reconstituted enzymatic systems have provided mechanistic insights into RNA-directed DNA methylation, the main pathway catalysing de novo methylation in plants. A better understanding of the regulatory mechanisms will enable locus-specific manipulation of the DNA methylation status. CRISPR-dCas9-based epigenome editing tools are being developed for this goal. Given that DNA methylation patterns can be stably transmitted through meiosis, and that large phenotypic variations can be contributed by epimutations, epigenome editing holds great promise in crop breeding by creating additional phenotypic variability on the same genetic material.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics 利用单细胞和空间转录组学分析细胞特征和组织结构
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-08-21 DOI: 10.1038/s41580-024-00768-2
Gunsagar S. Gulati, Jeremy Philip D’Silva, Yunhe Liu, Linghua Wang, Aaron M. Newman
{"title":"Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics","authors":"Gunsagar S. Gulati, Jeremy Philip D’Silva, Yunhe Liu, Linghua Wang, Aaron M. Newman","doi":"10.1038/s41580-024-00768-2","DOIUrl":"https://doi.org/10.1038/s41580-024-00768-2","url":null,"abstract":"<p>Single-cell transcriptomics has broadened our understanding of cellular diversity and gene expression dynamics in healthy and diseased tissues. Recently, spatial transcriptomics has emerged as a tool to contextualize single cells in multicellular neighbourhoods and to identify spatially recurrent phenotypes, or ecotypes. These technologies have generated vast datasets with targeted-transcriptome and whole-transcriptome profiles of hundreds to millions of cells. Such data have provided new insights into developmental hierarchies, cellular plasticity and diverse tissue microenvironments, and spurred a burst of innovation in computational methods for single-cell analysis. In this Review, we discuss recent advancements, ongoing challenges and prospects in identifying and characterizing cell states and multicellular neighbourhoods. We discuss recent progress in sample processing, data integration, identification of subtle cell states, trajectory modelling, deconvolution and spatial analysis. Furthermore, we discuss the increasing application of deep learning, including foundation models, in analysing single-cell and spatial transcriptomics data. Finally, we discuss recent applications of these tools in the fields of stem cell biology, immunology, and tumour biology, and the future of single-cell and spatial transcriptomics in biological research and its translation to the clinic.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Far from the cytoplasmic crowd 远离细胞质人群
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-08-19 DOI: 10.1038/s41580-024-00774-4
Eytan Zlotorynski
{"title":"Far from the cytoplasmic crowd","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-024-00774-4","DOIUrl":"https://doi.org/10.1038/s41580-024-00774-4","url":null,"abstract":"Stresses induce de-crowding and fluidization of the cytoplasm, which promotes the formation of biomolecular condensates.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases 神经退行性疾病中自噬-溶酶体功能障碍的机制
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-08-06 DOI: 10.1038/s41580-024-00757-5
Ralph A. Nixon, David C. Rubinsztein
{"title":"Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases","authors":"Ralph A. Nixon, David C. Rubinsztein","doi":"10.1038/s41580-024-00757-5","DOIUrl":"https://doi.org/10.1038/s41580-024-00757-5","url":null,"abstract":"<p>Autophagy is a lysosome-based degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and aggregate-prone proteins. Their postmitotic nature and extremely polarized morphologies make neurons particularly vulnerable to disruptions caused by autophagy–lysosomal defects, especially as the brain ages. Consequently, mutations in genes regulating autophagy and lysosomal functions cause a wide range of neurodegenerative diseases. Here, we review the role of autophagy and lysosomes in neurodegenerative diseases such as Alzheimer disease, Parkinson disease and frontotemporal dementia. We also consider the strong impact of cellular ageing on lysosomes and autophagy as a tipping point for the late-age emergence of related neurodegenerative disorders. Many of these diseases have primary defects in autophagy, for example affecting autophagosome formation, and in lysosomal functions, especially pH regulation and calcium homeostasis. We have aimed to provide an integrative framework for understanding the central importance of autophagic–lysosomal function in neuronal health and disease.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural biology and molecular pharmacology of voltage-gated ion channels. 电压门控离子通道的结构生物学和分子药理学。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-08-05 DOI: 10.1038/s41580-024-00763-7
Jian Huang, Xiaojing Pan, Nieng Yan
{"title":"Structural biology and molecular pharmacology of voltage-gated ion channels.","authors":"Jian Huang, Xiaojing Pan, Nieng Yan","doi":"10.1038/s41580-024-00763-7","DOIUrl":"https://doi.org/10.1038/s41580-024-00763-7","url":null,"abstract":"<p><p>Voltage-gated ion channels (VGICs), including those for Na<sup>+</sup>, Ca<sup>2+</sup> and K<sup>+</sup>, selectively permeate ions across the cell membrane in response to changes in membrane potential, thus participating in physiological processes involving electrical signalling, such as neurotransmission, muscle contraction and hormone secretion. Aberrant function or dysregulation of VGICs is associated with a diversity of neurological, psychiatric, cardiovascular and muscular disorders, and approximately 10% of FDA-approved drugs directly target VGICs. Understanding the structure-function relationship of VGICs is crucial for our comprehension of their working mechanisms and role in diseases. In this Review, we discuss how advances in single-particle cryo-electron microscopy have afforded unprecedented structural insights into VGICs, especially on their interactions with clinical and investigational drugs. We present a comprehensive overview of the recent advances in the structural biology of VGICs, with a focus on how prototypical drugs and toxins modulate VGIC activities. We explore how these structures elucidate the molecular basis for drug actions, reveal novel pharmacological sites, and provide critical clues to future drug discovery.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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