Volume 19 Issue 9, September 2017

Brown adipose tissue is a key metabolic organ that oxidizes fatty acids and glucose to generate heat. Through epigenomic analyses of multiple adipose depots, the transcription factor nuclear factor I-A (NFIA) is now shown to drive the brown fat genetic program through binding to lineage-specific cis-regulatory elements.

Cellular senescence, a cell-autonomous growth arrest program, also executes pleiotropic non-cell-autonomous activities through the senescence-associated secretory phenotype (SASP). The innate cGAS–STING DNA-sensing pathway is now shown to regulate senescence by recognizing cytosolic DNA and inducing SASP factors, uncovering an unexpected link between these two previously unrelated pathways.

Three-dimensional brain organoid models have come into the spotlight as in vitro tools to recapitulate complex features of the brain. Four recent papers now leverage current technologies to generate new flavours of brain organoids and address aspects of brain biology which, to date, have been challenging to explore.

Induced pluripotent stem cells derived from aged donors (A-iPSCs) usually show genomic instability that affects their utility and raises concerns about their safety. Now, a study highlights the importance of ZSCAN10-dependent recovery of glutathione–ROS homeostasis in counteracting the genomic defects in A-iPSCs.

Cancer treatments often focus on killing tumour cells through apoptosis, which is thought to typically require mitochondrial outer membrane permeabilization (MOMP) and subsequent caspase activation. A study now shows that MOMP can trigger TNF-dependent, but caspase-independent cell death, suggesting a different approach to improve cancer therapy.

Flores et al. show that hair follicle stem cells rely on the production of lactate via the LDHA enzyme to become activated. Inducing Ldha through Mpc1 inhibition or Myc activation successfully reactivates the hair cycle in quiescent follicles.

Schell et al. demonstrate that inactivation of the mitochondrial pyruvate carrier in mouse and fly intestinal stem cells (ISCs) locks the cell into a glycolytic metabolic program and promotes the expansion of the stem cell compartment.

Skamagki et al. show that pluripotency factor ZSCAN10 is poorly expressed in iPSCs derived from aged donors, and its addition during reprogramming restores the DNA damage response and genomic stability through normalization of ROS–glutathione levels.

Zihni et al. discover a role for Cdc42–MRCK signalling in establishing contractility at the apical pole, which in turn controls epithelial polarity in mammalian cells and Drosophila photoreceptors.

Glück et al. find that the DNA-sensing component cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments produced in senescent cells leading to STING-mediated production of SASPs, which promotes paracrine senescence.

Schalbetter et al. show by Hi-C and modelling that mitotic chromosome compaction in budding yeast occurs by cis-looping of chromatin, and reveal distinct roles for cohesin and condensin depending on chromatin context.

Hiraike et al. identify nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat. NFIA activates cell-type-specific enhancers prior to differentiation and facilitates PPARγ binding to regulate the brown fat gene program.

Horton et al. show that early Crebbp loss in haematopoietic progenitors results in a defective p53-mediated DNA damage response, leading to the accumulation of epigenetic and genetic alterations, which promote the onset of lymphoid malignancies.

Grelet et al. find that hnRNP E1 release from PNUTS pre-RNA in response to TGFβ generates a lncRNA that acts as competitive sponge for miR-205, promoting epithelial–mesenchymal transition in cancer.

Tait and colleagues show that caspase-independent cell death induced by mitochondrial permeabilization stimulates NF-κB activity through downregulation of inhibitor of apoptosis, and enhances anti-tumour effects.