Volume 19 Issue 5, May 2017

A feature of the cell cycle is that the events of one cycle must be reset before the next one begins. A study now shows that the replication machinery is removed from fully replicated DNA by a conserved ubiquitin- and CDC48 (also known as p97)-dependent pathway. This explains how eukaryotic chromosomes are returned to the unreplicated state.

The metabolic transition from mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis is critical for somatic reprogramming of induced pluripotent stem cells (iPSCs). SIRT2 has now been established as a previously unknown regulator of this metabolic transition during somatic reprogramming by controlling the acetylation status of glycolytic enzymes.

Dysfunctional cells are eliminated from epithelial monolayers by a process known as cell extrusion to maintain tissue homeostasis. Normal epithelial cells are now shown to induce the extrusion of oncogene-transformed cells by inducing metabolic changes in the oncogene-expressing cells through PDK4-mediated inhibition of PDH and mitochondrial metabolism.

The role of the epithelial-to-mesenchymal transition in tumour progression remains a topic of intense debate. Now, data on the role of Zeb1 in the metastatic spread of pancreatic cancer clarify apparently conflicting views by revealing context-specific, differential use of individual epithelial-to-mesenchymal transition transcription factors in cancer cell dissemination.

The non-essential amino acids serine and glycine are critical for proliferative metabolism. A study in Nature now finds that dietary serine and glycine deprivation inhibits growth of some tumours. Whether this dietary intervention is effective depends on both the oncogenic context and tumour tissue of origin.

Chatzinikolaou et al. show that the nucleotide excision repair complex ERCC1–XPF cooperates with the chromatin organizer CTCF, cohesin subunits and ATRX to facilitate the silencing of a subset of imprinted genes in the developing liver.

Reilein et al. demonstrate that Drosophila ovarian follicle stem cells (FSCs) produce either proliferative follicle cells or quiescent escort cells, depending on which position they occupy in the germarium and in response to graded Wnt signalling.

Cha et al. show that SIRT2 suppression by miR-200c enhances acetylation levels and enzymatic activities of glycolytic enzymes and contributes to metabolic reprogramming of human induced pluripotent stem cells and human embryonic stem cells.

Damm et al. demonstrate that trunk neural crest cell migration to the dorsal aorta in zebrafish is regulated by platelet-derived growth factor (PDGF) signalling and required for haematopoietic stem cell (HSC) specification.

The Cdc45–MCM–GINS (CMG) complex is needed for DNA replication, but how CMG dissociates from DNA in higher eukaryotes is not clear. Sonneville et al. now characterize pathways for CMG dissociation and replication termination in worm and frog.

Jiang et al. show that the microcephaly-associated protein ASPM and katanin form a complex that binds microtubule minus ends and can sever microtubules and block microtubule minus-end elongation to control spindle pole dynamics.

Saade et al. show that Shh activation promotes symmetric pericentrin-mediated docking of PKA to centrosomes and the expansion of the motor neuron progenitor pool through symmetric proliferative divisions.

Sah and colleagues show that the volume-sensitive ion channel SWELL1 regulates adipocyte insulin-PI(3)K-AKT2 signalling, glucose uptake and lipid content through interactions with GRB2/Cav1.

Adding to the recent debate on the role of epithelial–mesenchymal transition (EMT) in cancer cell invasion and metastasis, Brabletz and colleagues show that the EMT-inducing transcription factor Zeb1 drives pancreatic tumorigenesis and metastasis.

Fujita et al. find that normal epithelial cells induce metabolic changes in adjacent transformed cells, causing their apical extrusion. The effect is conveyed non-cell-autonomously and relies on PDK4-mediated inhibition of mitochondrial function.

Chen et al. generate lung bud organoids from human pluripotent stem cells that recapitulate early lung development, such as branching airway formation and early alveolar structures, which could potentially be used to model lung disease.

Lin and Wang show that methionine deprivation reprogrammes bacterial metabolism to regulate host mitochondrial dynamics and lipid metabolism in Caenorhabditis elegans through nuclear receptor and Hedgehog signalling.

Porpiglia et al. use single-cell mass cytometry to analyse surface markers and key myogenic transcription factors of skeletal muscle stem cells during homeostasis and repair, and identify previously unrecognized myogenic progenitor cell populations.

Turco et al. derive long-term genetically stable organoids from normal endometrium and the decidua that recapitulate characteristics of in vivo uterine glands, respond to hormones and differentiate into secretory and ciliated endometrial cells.