title: Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons.
abstract: This article is part of a Special Issue "Estradiol and Cognition". Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic "makeup" of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics.
authors.affiliation: Department of Basic and Clinical Neuroscience, Cell and Behaviour Unit, The James Black Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: Carole
authors.initials: C
authors.lastname: Shum
authors.affiliation: Department of Basic and Clinical Neuroscience, Cell and Behaviour Unit, The James Black Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK; Faculty of Engineering, Universidade do Porto, 4200-465 Porto, Portugal.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Macedo
authors.affiliation: Department of Basic and Clinical Neuroscience, Cell and Behaviour Unit, The James Black Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Warre-Cornish
authors.affiliation: Department of Basic and Clinical Neuroscience, Cell and Behaviour Unit, The James Black Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Cocks
authors.affiliation: Department of Basic and Clinical Neuroscience, Cell and Behaviour Unit, The James Black Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Price
authors.affiliation: Department of Basic and Clinical Neuroscience, Cell and Behaviour Unit, The James Black Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. Electronic address: deepak.srivastava@kcl.ac.uk.
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000502:physiology; D008954:Models, Biological; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
chemical_list: D004967:Estrogens
keywords: 17β-estradiol; Autism spectrum disorders; Dendrite; Dendritic spines; Estrogen receptor; Neurodegenerative disease; Neurodevelopmental disorders; Psychiatric; Schizophrenia; Stem cells; Synapse