Table of contents

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The increasing complexity of the ubiquitin code pp579 - 586

Richard Yau & Michael Rape


Yau and Rape discuss recent advances in our understanding of the many variations in ubiquitin chain topology and how these mediate ubiquitin-dependent signalling in the cell.


News and Views

Stem cell heterogeneity revealed pp587 - 589

Marianne S. Andersen & Kim B. Jensen


The skin forms a protective, water-impermeable barrier consisting of heavily crosslinked epithelial cells. However, the specific role of stem cells in sustaining this barrier remains a contentious issue. A detailed analysis of the interfollicular epidermis now proposes a model for how a composite of cells with different properties are involved in its maintenance.

See also: Article by Sada et al.

PGC1α drives a metabolic block on prostate cancer progression pp589 - 590

Martina Wallace & Christian M. Metallo


Metabolic rewiring is essential for cancer cell survival. PGC1α, a transcriptional co-activator that is downregulated in prostate cancer, is now shown to control prostate cancer metabolism by activating an oxidative metabolic program that prevents tumour growth and metastatic dissemination.

See also: Article by Torrano et al.

Primary cilia mechanosensing triggers autophagy-regulated cell volume control pp591 - 592

Zsuzsanna Takacs & Tassula Proikas-Cezanne


The primary cilium and the process of autophagy are thought to be in a functionally reciprocal relationship. In further support of this link, fluid flow sensing by the primary cilium is now shown to induce autophagy, which in turn regulates the volume of kidney epithelial cells.

See also: Article by Orhon et al.

Replicating repetitive DNA pp593 - 594

Silvia Tognetti & Christian Speck


The function and regulation of repetitive DNA, the 'dark matter' of the genome, is still only rudimentarily understood. Now a study investigating DNA replication of repetitive centromeric chromosome segments has started to expose a fascinating replication program that involves suppression of ATR signalling, in particular during replication stress.

See also: Letter by Aze et al.



Medial HOXA genes demarcate haematopoietic stem cell fate during human development pp595 - 606

Diana R. Dou, Vincenzo Calvanese, Maria I. Sierra, Andrew T. Nguyen, Arazin Minasian, Pamela Saarikoski, Rajkumar Sasidharan, Christina M. Ramirez, Jerome A. Zack, Gay M. Crooks, Zoran Galic & Hanna K. A. Mikkola


Mikkola and colleagues show that medial HOXA gene expression, induced by retinoic acid signalling, marks the establishment of the definitive HSC fate and controls HSC identity and function.

Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal pp607 - 618

Eric M. Pietras, Cristina Mirantes-Barbeito, Sarah Fong, Dirk Loeffler, Larisa V. Kovtonyuk, SiYi Zhang, Ranjani Lakshminarasimhan, Chih Peng Chin, José-Marc Techner, Britta Will, Claus Nerlov, Ulrich Steidl, Markus G. Manz, Timm Schroeder & Emmanuelle Passegué


Passegué and colleagues reveal that pro-inflammatory IL-1 accelerates cell division and induces PU.1-mediated differentiation of HSCs into myeloid cells, whereas chronic IL-1 exposure compromises HSC function.

Defining the cellular lineage hierarchy in the interfollicular epidermis of adult skin pp619 - 631

Aiko Sada, Fadi Jacob, Eva Leung, Sherry Wang, Brian S. White, David Shalloway & Tudorita Tumbar


Using long-term lineage tracing and mathematical modelling, Tumbar and colleagues define two separate stem cell populations in the epidermis that are regionally clustered, molecularly distinct and show different proliferation dynamics.

See also: News and Views by Andersen & Jensen

Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation pp632 - 644

Thomas Welte, Ik Sun Kim, Lin Tian, Xia Gao, Hai Wang, June Li, Xue B. Holdman, Jason I. Herschkowitz, Adam Pond, Guorui Xie, Sarah Kurley, Tuan Nguyen, Lan Liao, Lacey E. Dobrolecki, Lan Pang, Qianxing Mo, Dean P. Edwards, Shixia Huang, Li Xin, Jianming Xu, Yi Li, Michael T. Lewis, Tian Wang, Thomas F. Westbrook, Jeffrey M. Rosen & Xiang H.-F. Zhang


Welte et al. report that mTOR signalling regulates G-CSF production and accumulation of myeloid-derived suppressor cells (MDSCs) to the tumour site, which promotes the tumour-initiating capacity of cancer cells by activating Notch signalling.

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis pp645 - 656

Veronica Torrano, Lorea Valcarcel-Jimenez, Ana Rosa Cortazar, Xiaojing Liu, Jelena Urosevic, Mireia Castillo-Martin, Sonia Fernández-Ruiz, Giampaolo Morciano, Alfredo Caro-Maldonado, Marc Guiu, Patricia Zúñiga-García, Mariona Graupera, Anna Bellmunt, Pahini Pandya, Mar Lorente, Natalia Martín-Martín, James David Sutherland, Pilar Sanchez-Mosquera, Laura Bozal-Basterra, Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Antonio Berenguer, Nieves Embade, Aitziber Ugalde-Olano, Isabel Lacasa-Viscasillas, Ana Loizaga-Iriarte, Miguel Unda-Urzaiz, Nikolaus Schultz, Ana Maria Aransay, Victoria Sanz-Moreno, Rosa Barrio, Guillermo Velasco, Paolo Pinton, Carlos Cordon-Cardo, Jason W. Locasale, Roger R. Gomis & Arkaitz Carracedo


Torrano et al. use bioinformatics analyses to identify PGC1α as a transcriptional regulator of a metabolic program downstream of ERRα that opposes metastatic dissemination in prostate cancer.

See also: News and Views by Wallace & Metallo

Primary-cilium-dependent autophagy controls epithelial cell volume in response to fluid flow pp657 - 667

Idil Orhon, Nicolas Dupont, Mohamad Zaidan, Valérie Boitez, Martine Burtin, Alain Schmitt, Thierry Capiod, Amandine Viau, Isabelle Beau, E. Wolfgang Kuehn, Gérard Friedlander, Fabiola Terzi & Patrice Codogno


Orhon et al. report that primary-cilium-mediated fluid flow sensing triggers autophagy through LKB1–AMPK–mTOR signalling, and thereby controls the volume of kidney epithelial cells.

See also: News and Views by Takacs & Proikas-Cezanne



Chromosome missegregation during anaphase triggers p53 cell cycle arrest through histone H3.3 Ser31 phosphorylation pp668 - 675

Edward H. Hinchcliffe, Charles A. Day, Kul B. Karanjeet, Sela Fadness, Alyssa Langfald, Kevin T. Vaughan & Zigang Dong


Chromosome missegregation can lead to p53 activation to block proliferation of aneuploid cells. Hinchcliffe, Dong and colleagues find that generation and spreading of a histone H3.3 Ser31 phosphorylation mark mediates this response.

Avoiding artefacts when counting polymerized actin in live cells with LifeAct fused to fluorescent proteins pp676 - 683

Naomi Courtemanche, Thomas D. Pollard & Qian Chen


Pollard and colleagues demonstrate in vitro and in fission yeast that the LifeAct actin probe can affect actin filament nucleation and dynamics and perturb actin-dependent cellular processes unless low concentrations are used.

Centromeric DNA replication reconstitution reveals DNA loops and ATR checkpoint suppression pp684 - 691

Antoine Aze, Vincenzo Sannino, Paolo Soffientini, Angela Bachi & Vincenzo Costanzo


Costanzo and colleagues find, by reconstitution of repetitive centromeric DNA replication in Xenopus egg extracts, that replication is facilitated by suppression of ATR-mediated checkpoint signalling and formation of DNA loop structures.

See also: News and Views by Tognetti & Speck

Sister chromatid resolution is an intrinsic part of chromosome organization in prophase pp692 - 699

Kota Nagasaka, M. Julius Hossain, M. Julia Roberti, Jan Ellenberg & Toru Hirota


The imaging of individually labelled sister chromatids allows Nagasaka et al. to conclude that mitotic sister chromatin resolution begins in prophase and depends on the activity of topoisomerase II and condensin II, but not on cohesin dissociation.


Technical Report

Self-organization of the human embryo in the absence of maternal tissues pp700 - 708

Marta N. Shahbazi, Agnieszka Jedrusik, Sanna Vuoristo, Gaelle Recher, Anna Hupalowska, Virginia Bolton, Norah M. E. Fogarty, Alison Campbell, Liani G. Devito, Dusko Ilic, Yakoub Khalaf, Kathy K. Niakan, Simon Fishel & Magdalena Zernicka-Goetz


Zernicka-Goetz and colleagues report an in vitro culture system that recapitulates hallmarks of human embryo morphogenesis before gastrulation, including formation of the pro-amniotic cavity and appearance of the prospective yolk sac.



Corrigendum: A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation p709

Xinjian Li, Xu Qian, Li-Xia Peng, Yuhui Jiang, David H. Hawke, Yanhua Zheng, Yan Xia, Jong-Ho Lee, Gilbert Cote, Hongxia Wang, Liwei Wang, Chao-Nan Qian & Zhimin Lu


Corrigendum: SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture p709

Manuel Hilbert, Akira Noga, Daniel Frey, Virginie Hamel, Paul Guichard, Sebastian H. W. Kraatz, Moritz Pfreundschuh, Sarah Hosner, Isabelle Flückiger, Rolf Jaussi, Mara M. Wieser, Katherine M. Thieltges, Xavier Deupi, Daniel J. Müller, Richard A. Kammerer, Pierre Gönczy, Masafumi Hirono & Michel O. Steinmetz