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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.
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.
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.
It is well documented that polyploid cells exist in mammalian tissues such as the placenta and liver, but their function and the mechanisms for their formation have remained elusive. Two studies now identify a role for atypical E2F transcription factors in promoting polyploidy in mammals and challenge present theories about the function of polyploidy.
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.
Blanpain and colleagues use inducible genetic lineage tracing to identify and follow the progenitors responsible for the development of the prostate glandular epithelium. They find that multipotent progenitors are initially able to differentiate into the three lineages that make up the prostate, with a later switch to distinct pools of unipotent basal and luminal stem cells.
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.
Centrosomes consist of two centrioles surrounded by pericentriolar material (PCM) that nucleates microtubules. The PCM has been considered as amorphous but, using subdiffraction fluorescence imaging, Pelletier and colleagues now reveal the organized structure of human PCM.
Centrosomes, the microtubule nucleation centre of most cells, consist of two centrioles surrounded by pericentriolar material (PCM). The PCM has been considered as amorphous but, using subdiffraction fluorescence microscopy approaches, Agard and colleagues now reveal the organized structure of the PCM of Drosophila centrosomes.
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.
It is not fully understood how polyploidy is regulated in mammals, as the liver is one of only a few tissues in which it occurs. De Bruin and colleagues demonstrate that gene repression through the E2F8 transcription factor, antagonized by E2F1, is required for polyploidization in mice. They also find that loss of polyploidy does not influence liver differentiation or regeneration.
In mammals, polyploidy is only seen in liver hepatocytes and in trophoblast giant cells in the placenta. Leone and colleagues now show that ploidy is controlled in an antagonistic fashion by canonical E2F transcriptional activators and atypical E2F7 and E2F8 repressors, through the control of G2/M-associated genes.
Wagner and colleagues show that cancer cell survival during liver cancer initiation depends on inhibition of c-Fos-induced apoptosis, through the repression of survivin expression by c-Jun and SIRT6.
Kang and colleagues show that the transcription factor Elf5 controls the epithelial–mesenchymal transition (EMT) during development and in metastasis, by repressing the expression of Snail2/Slug, a key EMT-inducing factor.
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.
