Volume 21 Issue 12, December 2019

In mammals, a circadian timing system composed of a master clock in the brain’s suprachiasmatic nucleus and oscillators in peripheral organs drives daily rhythms of behavior and physiology. A study now reveals that the periodic oxidation of the CLOCK protein enhances the amplitude of cyclic gene expression and affects the daily rhythms of behavior.

Tendons have limited regenerative potential, and injuries often cause scarring. A study now identifies a tendon stem cell population that contributes to regeneration and a tendon fibro–adipogenic progenitor population involved in fibrosis.

Harnessing DNA repair pathways in genome editing In this Review, Yeh, Richardson and Corn discuss the DNA repair pathways that underlie genome editing and recent improvements and strategies to yield desired genomic alterations in cells and organisms.

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.

Using single-cell transcriptomics and in vivo injury models, Harvey et al. identify a Tppp3⁺Pdgfra⁺ stem cell population in the tendon sheath and demonstrate the role of PDGFRα signalling in regeneration and fibrosis.

Ling and Sauka-Spengler reveal chromatin and transcriptional landscapes that regulate the early specification of vagal neural crest cells during the development of the enteric nervous system in chicken.

The T-box factors Eomes and Brachyury activate mesoderm and endoderm programs by establishing accessible chromatin at mesoderm and endoderm enhancers, and bind and repress enhancers of pluripotency and neuroectoderm genes.

Perry and Morioka et al. show that the chloride transporter SLC12A2 regulates apoptotic cell uptake by phagocytes and, together with SLC12 kinases WNK1, OSR1 and SPAK, this pathway maintains an anti-inflammatory gene signature.

Mercey et al. demonstrate that without deuterosomes, multiciliated cells still develop the proper number of centrioles with normal step-wise kinetics, independent of the growing platform.

Pei et al. show that rhythmic redox signalling controls CLOCK through endogenous H₂O₂ oscillations via reversible oxidative modifications, and that p66^Shc modulates the rhythm of H₂O₂ levels.

Chen et al. show that, after serum or lysophosphatidic acid stimulation, RhoA dissociates rhophilin and NF2/Kibra from STRIPAK to control MST1, MST2 and MAP4Ks to regulate Hippo signalling.

Cai et al. show that YAP forms liquid-like condensates in the nucleus that compartmentalize YAP’s DNA binding cofactors and transcription co-activators to induce transcription of YAP-specific proliferation genes.

Translational reprogramming during asparagine restriction, via activated MAPK signalling and enhanced translation of activating transcription factor 4 (ATF4) mRNA in melanoma and pancreatic cancer cells, provide a survival advantage.

Zhu et al. show that, in response to growth factors, TBKBP1 recruits TBK1 to promote its activation by PKCθ, thereby facilitating mTORC1 activation, tumour-mediated immunosuppression and tumourigenesis.