Provided are compositions and methods that relate to cultured neurons. The cultured neurons can either have or not have genetic mutations that are characteristic of Parkinson's disease (PD). The cultured neurons are generated from induced pluripotent stem cells made from human fibroblasts that are obtained from individuals with and without PD. Cultured neurons without genetic mutations characteristic of PD are dopaminergic neurons that exhibit specific dopamine uptake are provided. Also provided is a method for identifying a test agent as a potential candidate for reducing the severity of PD. The method involves obtaining cells of neural lineage derived from cells obtained from an individual who has PD and measuring the effects of the test agents on dopaminer-characteristics, including specific dopamine uptake, monoamine oxidase (MAO) transcription levels, protein and/or activity levels of estrogen-related receptors, and combinations thereof. An increase in specific dopamine uptake, inhibition of MAO transcription or decrease in the level and/or activity of estrogen-related receptors caused by the agent can be used to identify the agent as a potential candidate for reducing the severity of PD.
Provided herein are compositions and methods for generation of naive human pluripotent stem cells. The method comprises incubation of iPSCs under 5% Oin a medium comprising 5% glucose, an MEK inhibitor, a GSK3β inhibitor, human leukemia inhibitory factor (LIF), human insulin and Torin 1. The method does not need any other inhibitors or transgene expression. The naive human pluripotent cells can be used to generate a large amount of mature human cells from all three germ layers in host non-human animals.
"This is the first time that human dopamine neurons have ever been generated from Parkinson's disease patients with parkin mutations," says Jian Feng, PhD, professor of physiology and biophysics in the UB School of Medicine and Biomedical Sciences and the study's lead author.
is the first time that human dopamine neurons have ever been generated from Parkinson's disease patients with parkin mutations," said Dr. Jian Feng, professor of physiology and biophysics in the UB School of Medicine and Biomedical Sciences and the study's lead author, The Digital Journal reported.