Volume 17 Issue 8, August 2015

Mitotic chromosome condensation has fascinated biologists since Flemming's early illustrations of mitosis in the late nineteenth century. Now — 130 years later — chromatid condensation is reconstituted in vitro with the minimum components. The results are remarkably and beautifully simple, requiring only core histones, three histone chaperones, topoisomerase II and condensin I.

Modelling organs in culture has great potential to improve our understanding of development, organogenesis and disease. While some endodermal derived organs have been modelled, the corpus region of the stomach, where acid-producing cells reside, remained an invincible target. A 60-day differentiation protocol now enables the generation of functional acid-producing cells in culture, conquering the challenge.

Activator E2Fs and Myc cooperate as master regulators of proliferation. A new study sheds light on one of the fundamental questions in cancer biology: how do oncogenic changes, such as Retinoblastoma (RB)-mutation, modify E2F and Myc activity?

Forbes and colleagues report on a population of hepatic progenitor cells that regenerate the adult liver in a mouse model where more than 98% of all hepatocytes are irreversibly damaged.

Noguchi and colleagues report the generation of stomach-like tissue from mouse embryonic stem cells. They show that the tissue contains all stomach-specific cell types and secretes acid and digestive enzyme.

Cowan and colleagues report a method to generate mature endothelial or vascular smooth muscle cells from human pluripotent stem cells with high efficiency and purity.

Lopez-Otin and colleagues report that NF-κB signalling hyperactivation in progeria syndrome fibroblasts inhibits their reprogramming into iPS cells. Blockade of this pathway or the downstream factor DOTL1 rescues senescence-related phenotypes.

Hirano and colleagues have reconstituted mitotic chromatin condensation in cell-free extracts using six purified factors, including histone chaperones, topoisomerase II and condensin I.

Hanafusa and Matsumato and colleagues find that LRRK1 is a substrate for PLK1 in mitosis. Phosphorylated LRRK1 in turn phosphorylates CDK5RAP2 to promote centrosomal microtubule nucleation and correct spindle orientation.

Leone and colleagues find that in intestinal crypt cells, Myc and E2F transcription factors control the transition into the G₂ phase of the cell cycle, but in the absence of Rb, Myc and E2f3a drive S phase entry and ectopic proliferation in vivo.

Campisi and colleagues show that the MTOR inhibitor rapamycin blocks the senescence-associated secretory phenotype (SASP) by inhibiting translation of IL1A, which prevents senescent fibroblasts from promoting tumour growth.

Romagnolo and colleagues report that Atg7 deficiency has a tumour-suppressive role in the intestinal epithelium, by inducing a microbiome-influenced immune response and inhibiting tumour growth through p53- and AMPK-related mechanisms.

In an effort by several research groups, a genome-wide RNAi-based screen presents a list of validated genes involved in cilia assembly and maintenance, and reveals previously unidentified ciliopathy factors.