Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs.

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This chapter examines the illegal wildlife trade (IWT) in the Mekong, with particular attention to how political economic factors and legal structures shape actors’ interests and incentives. The current literature on wildlife trafficking mainly attributes wildlife protection failures to weak enforcement. However, this literature has paid little attention to the underlying factors that contribute to the weak enforcement of wildlife laws. This chapter applies a political economy analysis to better understand the role of each actor from the point of wildlife sourcing to end consumption. It also explains why effectively enforcing wildlife laws is difficult and is often not in the interest of wildlife officials. This chapter thus examines why actors along IWT supply chains engage in illegal activities and do not abide by conservation laws. With rising demand for wildlife products, particularly because of increasing economic prosperity, the survival of many endangered species is under threat. Despite growing calls for total bans of wildlife trade or trade regulations to prevent overharvesting, these frequently fail to achieve conservation goals if they do not consider the local political economy context. This chapter focuses on the global IWT hotspots of Vietnam, Laos, and Cambodia, analyzing how legal frameworks shape local political economies and showing why IWT is a pervasive problem in the region.