Probing disorders of the nervous system using reprogramming approaches.
The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges.
Department of Stem Cells and Regenerative Medicine, Eli and Edythe Broad, CIRM Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, CA, USA ichida@usc.edu evangelos.kiskinis@northwestern.edu.
Justin K
JK
Ichida
The Ken and Ruth Davee Department of Neurology & Clinical Neurological Sciences and Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA ichida@usc.edu evangelos.kiskinis@northwestern.edu.
Evangelos
E
Kiskinis
D000818:Animals; D065150:Cellular Reprogramming; D006801:Humans; D008959:Models, Neurological; D009422:Nervous System Diseases / Q000378:metabolism / Q000628:therapy; D009474:Neurons / Q000166:cytology / Q000378:metabolism
directed differentiation; disease modeling; neurologic disorder; neuronal development