Volume 25 Issue 8, August 2023

Reprogramming of somatic cells is an inherently inefficient process. A new study has now identified histone H3K36 methylation as a crucial reprogramming barrier that operates downstream of TGFβ signalling. Global inhibition of H3K36 methylation induced PRC2-dependent silencing of mesenchymal genes and dramatically increased reprogramming efficiency.

A fast protocol for chemical cellular reprogramming reveals a diapause-like state, endogenous retrovirus activation and barriers to cell-fate transitions on the way to pluripotency. The system offers insights into manipulation of cellular regeneration and rejuvenation, two processes with great therapeutic potential.

Pioneer transcription factors bind closed chromatin regions, alter local accessibility and activate target genes. A study reveals that the SOX9 transcription factor drives cell fate switching by activating hair follicle cell enhancers, while simultaneously repressing epidermal enhancers via sequestration of epigenetic factors.

In many species, a mother’s environment can impact offspring’s metabolism, but the mechanisms that mediate such intergenerational effects are unclear. In this issue, a study finds that the provisioning of a sphingolipid from mothers to offspring drives changes in offspring metabolism that protect against neuronal damage.

Molecular insight into mechanisms that mediate the selective autophagy of lipid droplets (that is, lipophagy) has been lacking. This study identifies spartin, a protein mutated in a complex hereditary spastic paraplegia called Troyer syndrome, as a receptor that targets lipid droplets to the lysosome for degradation.

Sphingomyelin synthase 2 foci assemble at the leading edge of the basal membrane in migrating cells, and these foci eventually become sites of migrasome formation. Conversion of ceramide to sphingomyelin spurs migrasome growth and preserves the structural integrity of these organelles.

The Human BioMolecular Atlas Program (HuBMAP) presents its production phase: the generation of spatial maps of functional tissue units across organs from diverse populations and the creation of tools and infrastructure to advance biomedical research.

Chung et al. identify the protein spartin, linked to Troyer syndrome, as a lipophagy receptor for lipid droplet clearance in vitro and in vivo. The data suggest that impaired lipid droplet turnover may contribute to Troyer syndrome development.

Dai et al. show that the transcription factor ATFS-1 interferes with mitochondrial pre-initiation transcription complex assembly and promotes mitochondrial DNA repair, thereby reducing age-dependent mitochondrial DNA damage in Caenorhabditis elegans.

Hoetker et al. show that H3K36 methylation exerts a dual role in cell identity maintenance: it integrates TGFβ signals at mesenchymal targets to keep them active and prevents the activation of alternative lineage programmes via enhancer methylation.

Ghersi et al. report that haematopoietic stem and progenitor cell heterogeneity is established on the haemogenic endothelium level and is, at least in part, regulated by microRNA-128-mediated modulation of Wnt and Notch signalling.

Chen et al. develop a fast chemical reprogramming system that promotes the transition towards pluripotency through a unique diapause-like state.

Enkler et al. show that a pool of Arf1 at lipid droplets is implicated in mitochondrial ATP production control through regulation of fatty acid metabolism and acetyl-CoA transfer to mitochondria.

Liang et al. report mechanisms of migrasome biogenesis in migrating cells. They propose that sphingomyelin synthase 2 (SMS2) is required for migrasomes, first by localizing in stable puncta where they eventually form migrasome structures.

Yang, Gomez et al. show that the pioneer factor SOX9 regulates the switch from epidermal stem cell to hair follicle stem cell fate by binding and opening hair follicle enhancers, while recruiting epigenetic factors away from epidermal enhancers.

Wang et al. show that intestinal sphingosine-1-phosphate is transferred to oocytes and influences sphingolipid metabolism in the next generations. In the offspring, sphingosine-1-phosphate protects Caenorhabditis elegans neurons against axon fragility.

Zhang, Jiang and colleagues demonstrate that, independent of its role in innate immunity, STING can target and inhibit HK2 activity, thereby blocking tumour aerobic glycolysis and enhancing antitumour immune responses.

Chen, Neil, Tan, Rudraraju et al. use an induced trophoblast stem-cell-based model of SARS-CoV-2 infection and identify syncytiotrophoblasts as the cells targeted by the virus in the early placenta.