Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization
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 syste...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1411 |
| _version_ | 1797505334810509312 |
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| author | Ryan W. Tam Albert J. Keung |
| author_facet | Ryan W. Tam Albert J. Keung |
| author_sort | Ryan W. Tam |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T04:17:09Z |
| format | Article |
| id | doaj.art-946d16d9485a417193c116cae40200db |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:17:09Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-946d16d9485a417193c116cae40200db2023-11-23T07:58:49ZengMDPI AGCells2073-44092022-04-01119141110.3390/cells11091411Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene DesensitizationRyan W. Tam0Albert J. Keung1Chemical & Biomolecular Engineering Department, North Carolina State University, Campus Box 7905, Raleigh, NC 27695, USAChemical & Biomolecular Engineering Department, North Carolina State University, Campus Box 7905, Raleigh, NC 27695, USAGene 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.https://www.mdpi.com/2073-4409/11/9/1411dopaminegene desensitizationacute and chronicRNA-seqhuman embryonic stem cellmedium spiny neuron |
| spellingShingle | Ryan W. Tam Albert J. Keung Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization Cells dopamine gene desensitization acute and chronic RNA-seq human embryonic stem cell medium spiny neuron |
| title | Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization |
| title_full | Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization |
| title_fullStr | Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization |
| title_full_unstemmed | Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization |
| title_short | Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization |
| title_sort | human pluripotent stem cell derived medium spiny neuron like cells exhibit gene desensitization |
| topic | dopamine gene desensitization acute and chronic RNA-seq human embryonic stem cell medium spiny neuron |
| url | https://www.mdpi.com/2073-4409/11/9/1411 |
| work_keys_str_mv | AT ryanwtam humanpluripotentstemcellderivedmediumspinyneuronlikecellsexhibitgenedesensitization AT albertjkeung humanpluripotentstemcellderivedmediumspinyneuronlikecellsexhibitgenedesensitization |