How Human Induced Pluripotent Stem Cells-Derived Models can Advance our Understanding of Secretion Mechanisms in Physiological and Pathological Contexts?

The molecular architecture of differentiated cells is essential to ensure their specific functions and is supported by membrane trafficking. Defects in the intracellular organization and/or in protein transport contribute to various diseases such as neurological and cardiac diseases. In the recent years, human induced pluripotent stem cells (hiPSCs) have been used to model diseases. Indeed, pluripotent stem cells represent a powerful model to reveal differences in the organization and functional capacity of the secretory trafficking routes responsible for the complex morphology and specialized functions of differentiated cells. This review focuses on the need to conduct investigations of the membrane trafficking mechanisms, their regulation and defects in hiPSCs-derived models, such as neurons and cardiomyocytes, and highlights how powerful these models are to unravel cell-type specific properties. Some studies conducted in hiPSCs-derived models deciphering trafficking defects in pathological conditions are cited as examples. New advances in genome editing, intracellular tools, high-resolution microscopy and fast imaging are essential for studying membrane trafficking in hiPSCs, which will be discussed, as well as their current limitations and areas of improvement. Altogether, this review is intended to pave the way for interconnected comparative studies required to understand the mechanisms regulating protein transport in health and disease.