Reviews & Analysis

Machine learning is becoming a widely used tool for the analysis of biological data. However, for experimentalists, proper use of machine learning methods can be challenging. This Review provides an overview of machine learning techniques and provides guidance on their applications in biology.

This Review discusses our current understanding of cell cycle regulation, the functions of cell cycle checkpoints and how disruption of these finely tuned mechanisms is associated with cancer. Insights into these regulatory mechanisms are creating new opportunities for the treatment of cancer.

Deficiency in the protein kinase ATM — a master regulator of double-strand DNA breaks and stress responses — causes ataxia telangiectasia (A-T). Recent studies link A-T with other neurodegenerative disorders, and implicate reactive oxygen species, mitochondrial dysfunction, defects in proteostasis and metabolism, and increased poly(ADP-ribosyl)ation in the aetiology of A-T.

In cells, microtubules are dynamically assembled and disassembled at their growing (plus) tips. Recent insights into microtubule plus tip organization now pave the way for understanding the regulation of microtubule dynamics and for addressing how these dynamics allow microtubules to fulfil their vast repertoire of cellular functions.

Polycomb repressive complex 1 (PRC1) and PRC2 are important gene regulators in various physiological contexts, especially in development. Recent studies have uncovered the molecular mechanisms that enable mammalian PRC1 and PRC2 to identify their genomic target sites, modify chromatin properties and control transcription.

An emerging model of gene regulation posits that DNA, RNA and proteins form condensate nuclear compartments that facilitate cooperative interactions. This Review discusses how compartmentalization can lead to non-stoichiometric molecular interactions and behaviours in transcription, co-transcriptional and post-transcriptional RNA processing, and higher-order chromatin regulation.

Following their biogenesis, autophagosomes undergo maturation into degradative autolysosomes by fusing with late endosomes/lysosomes. This process — involving an array of molecular regulators of membrane dynamics — is essential for autophagic degradation, and its deregulation can lead to disease, including neurodegeneration, muscle diseases and cancer, and propagation of pathogens.

Insulin resistance is one of the earliest manifestations of several human diseases, including type 2 diabetes and cardiovascular disease. This Review discusses the causes of insulin resistance and recent insights into the underlying mechanisms, providing directions for the development of novel therapeutic strategies

Stem cells are well known to be controlled transcriptionally, but recent studies indicate that pluripotency, cell fate and differentiation depend on the regulation of translation and ribosome biogenesis by mTOR signalling, ribosome levels, and mRNA and tRNA features. Elucidating these stem cell regulatory mechanisms may increase our understanding of tumorigenesis.

Myopathies are genetically inherited diseases that affect the structure and/or function of skeletal muscles and often result in muscle degeneration (muscular dystrophy). This Review discusses our current understanding of the cellular and molecular mechanisms that underlie the most common of these pathologies, which provide key insights into muscle biology.

The orientation of cell divisions regulates tissue architecture and cell fate and depends on mitotic spindle positioning, which is controlled by intracellular and extracellular cues. Building on work in invertebrate systems, recent studies addressed how these mechanisms operate in vertebrates, and provided initial insights into their roles in vertebrate tissue development and homeostasis.

Expansion of short tandem repeats can impair RNA and protein function and cause diseases through four main mechanisms: transcription repression, RNA gelation and sequestration of RNA-binding proteins, protein gain of function, and repeat-associated non-AUG toxic translation. Synergy between these mechanisms exacerbates disease, but also offers promising therapeutic targets.

Bacteriophage anti-CRISPR proteins evolved to counter CRISPR–Cas-mediated immunity in prokaryotes. Recent structural studies have provided novel insights into the mechanisms and functions of anti-CRISPRs, and have increased the breadth of their use for biotechnology applications in eukaryotes.

Liver regeneration involves multiple cell types, including hepatocytes, hepatic stellate cells, endothelial cells and inflammatory cells. Recent studies have elucidated the interactions between these cells during regeneration as well as the mechanisms that regulate cell proliferation and fibrosis remodelling, and have uncovered macrophages as key players. Such findings can help design novel therapeutic approaches.

The canonical function of endocytosis is molecule internalization. Beyond this role, endocytic trafficking has emerged as a process central to the spatiotemporal regulation of cell signalling. Endocytic trafficking thus controls many cellular processes and tissue-wide properties, including cell migration and polarity, and its deregulation has been implicated in pathologies, particularly cancer.

Cells can sense various signals, including chemical, mechanical, geometric and electrical signals, and migrate towards or away from them. Such directed cell migration involves signal generation, sensing and transduction that eventually lead to polarized force generation. Deciphering the mechanisms underlying these processes is crucial to understanding cell migration in vivo.

Recent technological breakthroughs in mapping and visualizing chromatin contacts have considerably improved our understanding of 3D genome organization and function. This Review discusses the features, strengths and limitations of various methods of genome organization analysis, including sequencing-based techniques, microscopy-based techniques and computational and modelling approaches.

The cytoskeleton has been extensively implicated in regulating cell function and behaviour during development. This Review analyses the functional organization of cytoskeletal components in the early mouse embryo, and discusses key roles of the cytoskeleton during early mammalian embryogenesis, including regulation of cell fate specification and morphogenesis of the blastocyst.

High-resolution imaging technologies have revealed that all living organisms localize mRNAs in subcellular compartments, creating translation hotspots that locally tune gene expression. Insight has been gained into the mechanisms of mRNA transport and local mRNA translation, including into the role of messenger ribonucleoproteins and higher-order RNA granules in these processes.

Stromal progenitor cells contribute to the maintenance of tissue homeostasis in different organs. In vitro, these mesenchymal stromal cells (MSCs) can differentiate into many cell types. Recent omics and single-cell studies provide insights into the gene regulatory networks that drive lineage determination and cell differentiation, which has implications for the understanding of human diseases and for the development of cell-based therapies.