Volume 541 Number 7638

Editorials

News

News Features

News & Views

Phages make a group decision p.466

It emerges that phage viruses, which infect bacteria, use small peptides to communicate with each other. This observation of intercellular communication also reveals how viruses make a key developmental decision. See Article p.488

doi: 10.1038/nature21118

Optical transition seen in antihydrogen p.467

Precise measurements of antimatter systems might cast light on why the Universe is dominated by matter. The observation of a transition in an antihydrogen atom heralds the next wave of high-precision antimatter studies. See Letter p.506

doi: 10.1038/541467a

Earth's building blocks p.468

Earth grew by the accretion of meteoritic material. High-precision isotopic data reveal how the composition of this material changed over time, forcing revision of models of our planet's formation. See Letters p.521 & p.525

doi: 10.1038/541468a

Versatile gel assembly on a chip p.470

Materials called hydrogels have potential applications as scaffolds for tissue engineering, but methods are needed to assemble them into complex structures that mimic those found in nature. Just such a method has now been reported.

doi: 10.1038/nature21491

Unconventional translation in cancer p.471

Translation of RNA into proteins is a fundamental process for all cells. Analysis of a mouse model of skin cancer uncovers an atypical RNA-translation program that has a vital role in tumour formation. See Article p.494

doi: 10.1038/nature21115

Review

Articles

Structure of a CLC chloride ion channel by cryo-electron microscopy p.500

Some CLC proteins are channels that conduct chloride ions passively, whereas others are active co-transporters, a difference that has been hard to understand given their high degree of sequence homology; now, cryo-electron microscopy is used to determine the structure of a mammalian CLC channel, shedding light on this question.

doi: 10.1038/nature20812

Letters

The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα p.541

Cell fate perturbations underlie many human diseases, including breast cancer. Unfortunately, the mechanisms by which breast cell fate are regulated are largely unknown. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors. Breast cancer originates from this epithelium, but the molecular mechanisms that underlie breast epithelial hierarchy remain ill-defined. Here, we use a high-content confocal image-based short hairpin RNA screen to identify tumour suppressors that regulate breast cell fate in primary human breast epithelial cells. We show that ablation of the large tumour suppressor kinases (LATS) 1 and 2 (refs 5, 6), which are part of the Hippo pathway, promotes the luminal phenotype and increases the number of bipotent and luminal progenitors, the proposed cells-of-origin of most human breast cancers. Mechanistically, we have identified a direct interaction between Hippo and oestrogen receptor-α (ERα) signalling. In the presence of LATS, ERα was targeted for ubiquitination and Ddb1–cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation. Absence of LATS stabilized ERα and the Hippo effectors YAP and TAZ (hereafter YAP/TAZ), which together control breast cell fate through intrinsic and paracrine mechanisms. Our findings reveal a non-canonical (that is, YAP/TAZ-independent) effect of LATS in the regulation of human breast cell fate.

doi: 10.1038/nature20829