Emergent mechanical control of vascular morphogenesis.

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization.

Distal enhancers: new insights into heart development and disease.

Advances in genome research have provided an unprecedented opportunity to investigate the function of non-coding DNA regulatory regions that control transcription. Large-scale studies have recently identified hundreds of thousands of distal enhancer elements; their discovery has revealed new insights into the mechanistic details of how tissue-specific gene expression patterns are established and maintained during development. Emerging evidence indicates that lineage-specific transcription factors and chromatin regulators coordinate the activation of distal enhancers to ensure robust control of gene expression programs in a cell type-specific manner.

Staying alive: metabolic adaptations to quiescence.

Quiescence is a state of reversible cell cycle arrest that can grant protection against many environmental insults. In some systems, cellular quiescence is associated with a low metabolic state characterized by a decrease in glucose uptake and glycolysis, reduced translation rates and activation of autophagy as a means to provide nutrients for survival. For cells in multiple different quiescence model systems, including Saccharomyces cerevisiae, mammalian lymphocytes and hematopoietic stem cells, the PI3Kinase/TOR signaling pathway helps to integrate information about nutrient availability with cell growth rates.