Perspectives

Pan and Winkler review key recent advances in the rapidly developing field that focuses on the crosstalk between cancer and the nervous system and how this may be leveraged to inform rational design of cancer therapies.

Unfried and Ulitsky discuss recent advances in understanding how long noncoding RNAs expressed at much lower levels compared with their targets or cofactors overcome the stoichiometric disadvantages and exert their cellular functions.

Shi et al. discuss recent approaches for the discovery of small noncoding RNAs (sncRNAs), limitations associated with sncRNA expression analyses, and emerging methods for direct and simultaneous detection of multiple RNA modifications.

In this Perspective, Teichmann and colleagues present ongoing efforts from consortia of the Human Cell Atlas to harmonize and integrate data sources into a reference cell ontology and the contributions of cell ontologies to discovery.

In this Perspective, Börner et al. discuss initiatives by 16 consortia to construct a Human Reference Atlas (HRA) comprising reference organs linked to tables that name major anatomical structures, cell types, plus biomarkers (ASCT+B) and present examples of HRA usage.

In this Perspective, Fuxreiter and Vendruscolo discuss the fundamental nature of the droplet and amyloid states of proteins, the regulatory mechanisms controlling their formation, and the cellular functions associated with these condensed states.

RNA-targeting CRISPR. In this Perspective, Smargon, Shi and Yeo discuss the rapid development of the RNA-targeting CRISPR–Cas engineering system and highlight how this can be leveraged to further understand RNA biology.

In this Perspective, Lea and Niakan describe advances in CRISPR/Cas9 genome editing techniques and discuss ethical questions and potential clinical implications of this technology.

In this Perspective, Théry and co-authors discuss our current understanding of the biogenesis, secretion and uptake of exosomes and extracellular vesicles.

Jacobsen and Nerlov discuss the complexity, benefits and intrinsic limitations of studying haematopoiesis at the single-cell level using established and emerging technologies.

In this Perspective, Fässler and co-authors describe current models of how integrin adhesion molecules are activated and stabilised, and the importance of forces in this process.

In this Perspective, Dekoninck and Blanpain describe the characteristics of skin epithelial stem cells, their heterogeneity, clonal dynamics, crosstalk with other cells and remarkable plasticity during wound healing.

A history of autophagy. In this Perspective, Mizushima describes the leaps and bounds in the history of autophagy and discusses unanswered questions driving the field forward.

De novo generation of haematopoietic stem cells from different human pluripotent stem cell sources remains a high priority for haematology and regenerative medicine. At present, efficient derivation of functional haematopoietic stem cells with the capability for definitive in vivo engraftment and multi-lineage potential remains challenging. Here, we discuss recent progress and strategies to overcome obstacles that have thwarted past efforts. In addition, we review promising advances in the generation of mature blood lineages and the potential of induced pluripotent stem cells.

Visvader and Clevers discuss how stem cells from different tissues, such as the intestine, mammary gland and skeletal muscle, follow different strategies and hierarchies to maintain their complex, tissue-specific balance.

Microtubule polymerization is initiated by γ-tubulin containing complexes. Petry and Vale discuss factors involved in localizing and activating γ-tubulin at different locations in the cell.

Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. Recently, the identification of CSCs in endogenously developing mouse tumours has provided further support for this concept. Here I discuss the challenges in identifying CSCs, their dependency on a supportive niche and their role in metastasis, and propose that stemness is a flexible — rather than fixed — quality of tumour cells that can be lost and gained.

It has been proposed that the spindle assembly checkpoint detects both unattached kinetochores and lack of tension between sister kinetochores when sister chromatids are not attached to opposite spindle poles. However, here we argue that there is only one signal — whether kinetochores are attached to microtubules or not — and this has implications for our understanding of both chromosome segregation and the control of genomic stability.