Articles in 2012

Blanpain and colleagues use mouse models of activated Hedgehog signalling to analyse the temporal gene expression changes involved in basal cell carcinoma initiation. They show that tumour initiation involves activation of the Wnt pathway and reprogramming of the adult interfollicular epidermis tumour-initiating cells into a cell fate resembling that of embryonic hair follicle progenitor cells.

Both telomerase activity and NF-κB-driven inflammation occur in tumours, and NF-κB is known to upregulate telomerase levels. Tergaonkar and colleagues now find evidence for a reciprocal direct regulation of NF-κB-dependent gene transcription by telomerase, through an interaction between telomerase and the NF-κB p65 subunit.

Brown adipose tissue generates heat on exposure to cold temperatures. Stoffel and colleagues identify a cold-regulated pathway that increases levels of the transcriptional regulator Prdm16 to promote brown adipogenesis.

Rinkevich, Weissman and colleagues show that mesothelin-expressing cells from the mesothelium, an epithelial monolayer covering vertebrate cavities and internal organs, generate the fibroblasts and smooth muscle cells (FSMCs) essential for the development of internal organs. Using a genetic lineage tracing approach, they find that these cells participate in generating FSMCs and vasculature, with minimal contributions from neural crest or circulating cells.

The peripheral actin cortex in cells is essential for secretory vesicle exocytosis, but also acts as a barrier for vesicle release. Wollman and Meyer report that antigen activation triggers cyclical waves of Ca²⁺ and PtdIns(4,5)P₂ that promote N-WASP-mediated oscillations in F-actin polymerization. These permit secretion when F-actin levels are low, but impede exocytosis when F-actin levels are high.

Voinnet and colleagues show that autophagy targets RNAi components DICER and AGO2 for degradation when they are not bound to miRNA. The autophagy receptor NDP52 is required for this homeostatic regulation of the RNAi machinery. The authors also found that autophagy influences the post-translational regulation of DICER mRNA.

Guan and colleagues report that the Hippo pathway effector YAP regulates PI(3)K–mTOR signalling. YAP induces expression of the microRNA miR-29 to block PTEN expression, activating the PI(3)K pathway. Hippo and PI(3)K pathways thus converge to regulate cell growth and proliferation.

Epithelial to mesenchymal transition (EMT) is a fundamental process in both development and cancer progression. The transcription factor Elf5 is now reported as an upstream regulator of the key EMT inducer Snail2, and is shown to regulate the earliest known rewiring events required for tumour cell invasiveness and metastasis.

Michael Sheetz, James Spudich and Ronald Vale have been awarded the prestigious Albert Lasker Basic Medical Research Award for their work on cytoskeletal motors. Nature Cell Biology joins the scientific community in congratulating the awardees and in celebrating the importance of basic research in furthering scientific endeavour.

The pericentriolar material (PCM), the microtubule-organizing component of the centrosome, contains a multitude of proteins and is commonly described as an amorphous cloud surrounding the centrioles. However, the days of the PCM as an unstructured matrix are numbered. Using super-resolution microscopy, several reports have now revealed remarkable domain organization within the PCM.

Pluripotent stem cells (PSCs) express a distinctive set of microRNAs (miRNAs). Many of these miRNAs have similar targeting sequences and are predicted to regulate downstream targets cooperatively. These enriched miRNAs are involved in the regulation of the unique PSC cell cycle, and there is increasing evidence that they also influence other important characteristics of PSCs, including their morphology, epigenetic profile and resistance to apoptosis. Detailed studies of miRNAs and their targets in PSCs should help to parse the regulatory networks that underlie developmental processes and cellular reprogramming.

Chang and colleagues reveal that the poly(ADP-ribose) polymerase PARP16 participates in the endoplasmic reticulum (ER) stress response. They report that PARP16 is a transmembrane ER protein that PARsylates and activates PERK and IRE1α in response to ER stress.

Malliri and colleagues demonstrate that an apicobasal Rac activity gradient at cell–cell junctions is important for tight-junction assembly and establishment of apicobasal polarity. They show that this gradient is generated by the distinct spatial regulation of the Rac activator Tiam1 by β2-syntrophin and Par-3.

Lemischka and colleagues examine the effects of transient Nanog downregulation on the components of the pluripotent transcriptional regulatory network using single-cell gene expression analysis and modelling approaches. They observe that the initial changes induced by loss of Nanog are stochastic and reversible upon Nanog restoration, owing to the presence of feedback loops in the pluripotency network. Prolonged loss of Nanog compromises these feedback loops and reversion to pluripotency cannot be achieved upon Nanog restoration.