Reviews & Analysis

Mammalian cyclins and cyclin-dependent kinases (CDKs) have non-canonical, cell cycle-independent functions in processes such as transcription and DNA damage repair. Through these and other activities, they regulate cell death, differentiation, the immune response and metabolism.

Vertebrate cell volume is controlled to maintain homeostasis. Volume adjustment is achieved by regulating transmembrane transport of ions and small organic osmolytes through diverse transporters and channels (including volume regulated anion channels (VRACs)), which are also implicated in other physiological processes such as metabolite transport and apoptosis, as well as in pathology.

Some terminally differentiated cells have the capacity to de-differentiate or transdifferentiate under physiological conditions as part of a normal response to injury. Recent insights have been gained into the role of this cell plasticity in maintaining tissue and organ homeostasis, and this has important implications for cell-based therapies.

Metabolomics has been utilized extensively for the identification of single metabolites and their use as biomarkers. Owing to recent technical advances, it is now possible to use metabolomics to better understand whole metabolic pathways and to more precisely pinpoint the involvement of metabolites in physiology and pathology.

Signalling from the nucleus to mitochondria (NM signalling) is crucial for regulating mitochondrial function and ageing. It is initiated by nuclear DNA damage and controls genomic and mitochondrial integrity. Pharmacological modulation of NM signalling holds promise for improving lifespan and healthspan.

Adult muscles contain quiescent stem cells, known as satellite cells, which are activated upon injury, enabling muscle repair and replenishment of the stem cell pool. Recent studies have shed light on the molecular circuitry regulating satellite cell fate decision and the impairment of this circuitry during degenerative muscle diseases and ageing.

As most mitochondrial proteins are encoded in the nucleus, mitochondrial activity requires efficient communication between the nuclear and mitochondrial genomes. This is mediated by nucleus-to-mitochondria (anterograde), mitochondria-to-nucleus (retrograde) and mitonuclear feedback signalling, as well as the integrated stress response and extracellular communication, which regulate homeostasis and, consequently, healthspan and lifespan.

Circular RNAs (circRNAs) are produced from precursor RNA back-splicing. Recent findings reveal the complexity of the biogenesis of circRNAs and their cell type-specific expression. They also show that circRNAs can shape eukaryotic transcriptomes by sequestering microRNAs and by regulating transcription and interfering with splicing.

The ectopic expression of a defined set of transcription factors can experimentally reprogramme somatic cells into other cell types, including pluripotent cells. This method enables exploration of the molecular characteristics of pluripotency, cell specification, differentiation and cell fate stability, as well as their transcriptional and epigenetic regulation.

This year marks the tenth anniversary of the generation of induced pluripotent stem cells (iPSCs) by transcription factor-mediated somatic cell reprogramming. Takahashi and Yamanaka portray the path towards this ground-breaking discovery and discuss how, since then, research has focused on understanding the mechanisms underlying iPSC generation and on translating such advances to the clinic.

Recent advances in our understating of the molecular underpinnings of alternative primed- and naive-like pluripotent states in rodents and humans highlight potential functional benefits of naive pluripotency and identify key unanswered questions in this rapidly evolving field.

Quante and Bird propose that the epigenome is modulated by the recruitment of cell type-specific DNA-binding proteins to short, abundant sequence motifs. The regulation of gene expression may thus be simplified by tuning gene expression in multigene blocks.

The use of cultured human pluripotent stem cells (PSCs) to model human diseases has revolutionized the ways in which we study monogenic, multigenic and epigenetic disorders, by overcoming some of the limitations of animal models. PSC-based disease models are generated using various strategies and can be used for the discovery of new drugs and therapies.

Ephrin ligands and Eph receptor Tyr kinases are transmembrane proteins that elicit short-distance cell–cell signalling when they interact. As both Eph kinases and ephrins exist in various isoforms and function as receptors or ligands, this signalling evokes versatile responses, which regulate a plethora of morphogenetic and homeostatic processes.

Learning more about the biochemistry of protein prenylation (modification by isoprenoid lipids) and its functional effects on target CAAX proteins has provided opportunities for therapeutic intervention in a range of human diseases.

Members of the major facilitator superfamily are highly conserved transmembrane proteins that transport various small molecules, including nutrients, drugs, signalling molecules and waste products, across the plasma membrane. A novel model of their functional cycle provides insights into how these important transporters operate on the molecular level.

Collective cell migration has a crucial role during morphogenesis, wound healing and tissue renewal, and it is involved in cancer spreading. Recent studies highlight the importance of intercellular communication in this process: migration is driven by leader cells at the front, and follower cells communicate between them and with the leaders to improve the efficiency of collective movement.

The versatile RNA-degradation functions of the RNA exosome complex make it crucial for RNA biogenesis. It is now emerging that the nuclear exosome is a specific regulator of gene expression in different physiological processes, and that it has a role in transcription regulation and in maintaining genome stability.