Reviews & Analysis

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  • Tissue morphogenesis is instructed by the interplay of biochemical cues, mechanics and tissue geometry. Conceptually, these instructions can be deployed either deterministically, functioning as a pre-patterned programme for shape changes, or stochastically, whereby the shape emerges in a self-organized fashion. This Review discusses recent insights into how pre-patterned and stochastic tissue shaping are integrated during development.

    • Claudio Collinet
    • Thomas Lecuit
    Review Article
  • Insulin secretion from pancreatic β-cells is potently activated by an increase in glucose after feeding but other dietary components — amino acids, fatty acids, metabolites, α-cell-produced peptides and gastrointestinal tract hormones — further control this response. Deciphering this complex regulation is important to increase our understanding of pancreatic dysfunction in diabetes.

    • Jonathan E. Campbell
    • Christopher B. Newgard
    Review Article
  • Recent studies have provided novel insight into the biogenesis of long non-coding RNAs (lncRNAs) and their specific functions. The functions of lncRNAs vary from transcriptional and post-transcriptional gene regulation to the assembly and function of membraneless nuclear bodies, and are relevant to neuronal disorders, immune responses and cancer.

    • Luisa Statello
    • Chun-Jie Guo
    • Maite Huarte
    Review Article
  • Nicotinamide adenine dinucleotide (NAD+) is a central redox factor and enzymatic cofactor that functions in a plethora of cellular processes, including metabolic pathways and DNA metabolism, and affects cell fate and function. NAD+ levels gradually decline with age, and therapeutic elevation of NAD+ levels is being trialled for extending human healthspan and lifespan.

    • Anthony J. Covarrubias
    • Rosalba Perrone
    • Eric Verdin
    Review Article
  • Cellular senescence is characterized by a permanent proliferation arrest and the establishment of a senescence-associated secretory phenotype. This Review discusses the mechanisms of cellular senescence and induction of a senescence-associated secretory phenotype, recent insights into how senescence contributes to ageing, and the potential of senolytic and senomorphic therapies in ageing and associated diseases.

    • Raffaella Di Micco
    • Valery Krizhanovsky
    • Fabrizio d’Adda di Fagagna
    Review Article
  • Transcript elongation by RNA polymerase II can be perturbed by barriers such as promoter-proximal pausing and nucleosomes and by obstacles such as the replication machinery and DNA lesions. Recent studies revealed how different contexts of RNA polymerase II stalling are distinguished and resolved, and how unresolved stalling can cause genome instability.

    • Melvin Noe Gonzalez
    • Daniel Blears
    • Jesper Q. Svejstrup
    Review Article
  • Mechanical forces are important regulators of cell function and behaviour. This role is partly achieved through the modulation of cell metabolism, which, reciprocally, affects tissue mechanics. Unravelling the mechanisms of this crosstalk will increase our understanding of how cells interact with their microenvironment.

    • Patrizia Romani
    • Lorea Valcarcel-Jimenez
    • Sirio Dupont
    Review Article
  • Biomolecular condensates are membraneless molecular assemblies formed via liquid–liquid phase separation. They have a plethora of roles, ranging from controlling biochemical reactions to regulating cell organization and cell function. This article provides a framework for the study of condensate functions across these cellular length scales, offering to bring new understanding of biological processes.

    • Andrew S. Lyon
    • William B. Peeples
    • Michael K. Rosen
  • The mitochondrial proteome comprises ~1,000–1,500 nuclear-encoded and mitochondrial-encoded proteins. To ensure proper mitochondrial function, cells use multiple mechanisms of quality control that survey mitochondrial protein biogenesis, import and folding, and allow mitochondria to adapt to the changing needs as well as to respond to stresses that compromise proteostasis.

    • Jiyao Song
    • Johannes M. Herrmann
    • Thomas Becker
    Review Article
  • Various physiological processes including development and maintenance of epithelia, cell–cell fusion, neuronal function and immune responses rely on the establishment of direct cell–cell contacts. Despite their diversity, the different cell–cell interfaces can be viewed as specialized compartments that perform their distinct functions through common biophysical properties.

    • Brian Belardi
    • Sungmin Son
    • Daniel A. Fletcher
    Review Article
  • Glycosylation is the most abundant and diverse form of protein post-translational modification. Recent technical developments are enabling the dissection of the glycome in single cells, providing new insights into its regulation and roles in physiology and disease, and new possibilities for controlling glycosylation for therapy.

    • Katrine T. Schjoldager
    • Yoshiki Narimatsu
    • Henrik Clausen
    Review Article
  • Non-homologous DNA end joining (NHEJ) is the main repair pathway of DNA double-strand breaks. Recent studies show that synapsis — the crucial pairing of DNA ends — is performed by several mechanisms, and this insight can now be integrated with updates on the DNA end processing and ligation steps of NHEJ, and with NHEJ-related human diseases.

    • Bailin Zhao
    • Eli Rothenberg
    • Michael R. Lieber
    Review Article
  • The newest CRISPR–Cas genome editing technologies enable precise and simplified formation of crops with increased yield, quality, disease resistance and herbicide resistance, as well as accelerated domestication. Recent breakthroughs in CRISPR–Cas plant biotechnologies improve reagent delivery, gene regulation, multiplexed gene editing and directed evolution.

    • Haocheng Zhu
    • Chao Li
    • Caixia Gao
    Review Article
  • Cultured pluripotent stem cells (PSCs) acquire genetic changes — gains or losses of entire chromosomal regions, or point mutations, including in cancer-associated genes such as TP53. Recent work provides insights into the mechanisms of mutation and selection, which have implications for the use of human PSCs in regenerative medicine.

    • Jason Halliwell
    • Ivana Barbaric
    • Peter W. Andrews
    Review Article
  • The intestinal epithelium undergoes rapid turnover and is constantly exposed to hostile luminal contents. Recent insights from single-cell transcriptomics and organoid models have revealed that tissue repair is dependent on cell lineage plasticity and signals originating from different niche components.

    • Joep Beumer
    • Hans Clevers
    Review Article
  • This Review discusses the cell types, critical genes and transcription factors involved in bone development and repair. The dysfunctional cellular and molecular signalling that results in clinical bone disease is also outlined, thus informing the current state of science and clinical practice.

    • Ankit Salhotra
    • Harsh N. Shah
    • Michael T. Longaker
    Review Article
  • Dispensable, infected or neoplastic cells are removed by programmed cell death, including pathways for apoptosis, necroptosis and pyroptosis. Owing to differences in their mechanisms and physiological outcomes, these cell death pathways have traditionally been viewed as separate entities, but it has become clear that they are mechanistically and functionally connected.

    • Sammy Bedoui
    • Marco J. Herold
    • Andreas Strasser
    Review Article
  • The nucleolus is a membraneless organelle involved in ribonucleoprotein assembly, including ribosome biogenesis. Recent evidence indicates that the nucleolus is a biomolecular condensate that forms via liquid–liquid phase separation (LLPS), and insights from studies within the LLPS framework are increasing our understanding of the relationship between nucleolar structure and function.

    • Denis L. J. Lafontaine
    • Joshua A. Riback
    • Clifford P. Brangwynne
    Review Article
  • Histone variants differ from canonical histones in their genomic localization, regulation and function. Incorporation of histone variants endows specific genomic regions with unique features to fine-tune gene expression, contributing to animal development and disease pathogenesis.

    • Sara Martire
    • Laura A. Banaszynski
    Review Article
  • Human organoids are valuable models for the study of development and disease and for drug discovery, thus complementing traditional animal models. The generation of organoids from patient biopsy samples has enabled researchers to study, for example, infectious diseases, genetic disorders and cancers. This Review discusses the advantages, disadvantages and future challenges of the use of organoids as models for human biology.

    • Jihoon Kim
    • Bon-Kyoung Koo
    • Juergen A. Knoblich
    Review Article