Phenotypic plasticity and innovation - Oxford Scholarship
2) We show that hiPSC neurons allow compound screening for phenotypic profiling as well as for toxicity and side effect prediction (e.g. seizure) and discuss differences between mouse and human compound responses.
Global change and the evolution of phenotypic plasticity …
Individual genotypes can often form more than one phenotype; they show phenotypic plasticity. Phenotypic plasticity arises from environmental change. This chapter discusses how plasticity itself varies genetically. It shows that the genotype network concept can accommodate plasticity. More than that, the very existence of genotype networks facilitates the origin of new phenotypes through environmental change. The chapter discusses genetic assimilation and related phenomena. In genetic assimilation, a previously plastic phenotype loses this plasticity over time, and forms only one of its alternative phenotypes. Assimilation may be very widespread, thus supporting the notion that environmentally induced phenotypic change may be an important mode of evolutionary innovation. Plasticity is not necessarily good for adaptive evolution. It may even slow down adaptive evolution, depending on the phenotype considered.
Calcium regulation by the sarcoplasmic reticulum (SR) is a fundamental property of heart muscle that ensures efficient excitation-contraction (EC) coupling. SR calcium cycling is fully functional in the adult healthy myocardium but poorly utilised during development and disrupted during cardiac disease, indicating that SR contribution is a highly regulated and plastic function. Leveraging on the naïve and plastic properties of human induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs), we studied the effects of multicellular patterns and extracellular matrix (ECM) on the development of SR calcium cycling. We found that culture with human fibroblasts affects the EC coupling machinery in iPSC-CMs. Our data suggest the importance of heterocellularity and the ECM in the development of specialised features, particularly EC coupling, of adult cardiac muscle in naïve cardiac cells. This is not only relevant for the applications of iPSC-CMs in translational medicine and cardiovascular research but also to understand and target the plasticity of the EC coupling machinery in physiological conditions and during cardiac disease.