Chapter 25 - Hypothalamus and neuroendocrine diseases: The use of human-induced pluripotent stem cells for disease modeling

Abstract

The hypothalamus, which is part of the brain of all vertebrate animals, is considered the link between the central nervous system (CNS) and (i) the endocrine system via the pituitary gland and (ii) with our organs via the autonomic nervous system. It synthesizes and releases neurohormones, which in turn stimulate or inhibit the secretion of other hormones within the CNS, and sends and receives signals to and from the peripheral nervous and endocrine systems. As the brain region responsible for energy homeostasis, the hypothalamus is the key regulator of thermoregulation, hunger and satiety, circadian rhythms, sleep and fatigue, memory and learning, arousal and reproductive cycling, blood pressure, and heart rate and thus orchestrates complex physiological responses in order to maintain metabolic homeostasis. These critical roles implicate the hypothalamus in neuroendocrine disorders such as obesity, diabetes, anorexia nervosa, bulimia, and others. In this chapter, we focus on the use of human-induced pluripotent stem cells (hiPSCs) and their differentiation into hypothalamic neurons in order to model neuroendocrine disorders such as extreme obesity in a dish. To do so, we discuss important steps of human hypothalamus development, neuroendocrine diseases related to the hypothalamus, multiple protocols to differentiate hiPSCs into hypothalamic neurons, and severe obesity modeling in vitro using hiPSCs-derived hypothalamic neurons.