2022 journal article
Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization
CELLS, 11(9).
author keywords: dopamine; gene desensitization; acute and chronic; RNA-seq; human embryonic stem cell; medium spiny neuron
MeSH headings : Dopamine; Humans; Neurites; Neurons / physiology; Pluripotent Stem Cells; Receptors, Dopamine
TL;DR:
The dynamic responses of human stem cell-derived medium spiny neuron-like cells (hMSN- like cells) to dopamine are mapped and it is shown that these human neurons can reflect and capture cellular desensitization to chronic versus acute administration of dopamine.
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UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: May 23, 2022
Gene desensitization in response to a repeated stimulus is a complex phenotype important across homeostatic and disease processes, including addiction, learning, and memory. These complex phenotypes are being characterized and connected to important physiologically relevant functions in rodent systems but are difficult to capture in human models where even acute responses to important neurotransmitters are understudied. Here through transcriptomic analysis, we map the dynamic responses of human stem cell-derived medium spiny neuron-like cells (hMSN-like cells) to dopamine. Furthermore, we show that these human neurons can reflect and capture cellular desensitization to chronic versus acute administration of dopamine. These human cells are further able to capture complex receptor crosstalk in response to the pharmacological perturbations of distinct dopamine receptor subtypes. This study demonstrates the potential utility and remaining challenges of using human stem cell-derived neurons to capture and study the complex dynamic mechanisms of the brain.