Regulation of Adult Mammalian Neural Stem Cells and Neurogenesis by Cell Extrinsic and Intrinsic Factors

Tissue-specific stem cells give rise to new functional cells to maintain tissue homeostasis and restore damaged tissue after injury. To ensure proper brain functions in the adult brain, neural stem cells (NSCs) continuously generate newborn neurons that integrate into pre-existing neuronal networks. Proliferation, as well as neurogenesis of NSCs, are exquisitely controlled by extrinsic and intrinsic factors, and their underlying mechanisms have been extensively studied with the goal of enhancing the neurogenic capacity of NSCs for regenerative medicine. However, neurogenesis of endogenous NSCs alone is insufficient to completely repair brains damaged by neurodegenerative diseases and/or injury because neurogenic areas are limited and few neurons are produced in the adult brain. An innovative approach towards replacing damaged neurons is to induce conversion of non-neuronal cells residing in injured sites into neurons by a process referred to as direct reprogramming. This review describes extrinsic and intrinsic factors controlling NSCs and neurogenesis in the adult brain and discusses prospects for their applications. It also describes direct neuronal reprogramming technology holding promise for future clinical applications.