Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
Multiple genetic and environmental factors play a role in the development and progression of Parkinson's disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributo...
Guardado en:
Autores principales: | , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2013
|
Materias: | |
Acceso en línea: | https://doaj.org/article/b9d57f6d28de438980edd24634c769d1 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:b9d57f6d28de438980edd24634c769d1 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:b9d57f6d28de438980edd24634c769d12021-11-18T07:44:10ZPhenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.1932-620310.1371/journal.pone.0063862https://doaj.org/article/b9d57f6d28de438980edd24634c769d12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23724009/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple genetic and environmental factors play a role in the development and progression of Parkinson's disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD.Joanna A KoreckaRonald E van KesterenEva BlaasSonia O SpitzerJorke H KamstraAugust B SmitDick F SwaabJoost VerhaagenKoen BossersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63862 (2013) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Joanna A Korecka Ronald E van Kesteren Eva Blaas Sonia O Spitzer Jorke H Kamstra August B Smit Dick F Swaab Joost Verhaagen Koen Bossers Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. |
description |
Multiple genetic and environmental factors play a role in the development and progression of Parkinson's disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD. |
format |
article |
author |
Joanna A Korecka Ronald E van Kesteren Eva Blaas Sonia O Spitzer Jorke H Kamstra August B Smit Dick F Swaab Joost Verhaagen Koen Bossers |
author_facet |
Joanna A Korecka Ronald E van Kesteren Eva Blaas Sonia O Spitzer Jorke H Kamstra August B Smit Dick F Swaab Joost Verhaagen Koen Bossers |
author_sort |
Joanna A Korecka |
title |
Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. |
title_short |
Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. |
title_full |
Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. |
title_fullStr |
Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. |
title_full_unstemmed |
Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. |
title_sort |
phenotypic characterization of retinoic acid differentiated sh-sy5y cells by transcriptional profiling. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/b9d57f6d28de438980edd24634c769d1 |
work_keys_str_mv |
AT joannaakorecka phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT ronaldevankesteren phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT evablaas phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT soniaospitzer phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT jorkehkamstra phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT augustbsmit phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT dickfswaab phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT joostverhaagen phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling AT koenbossers phenotypiccharacterizationofretinoicaciddifferentiatedshsy5ycellsbytranscriptionalprofiling |
_version_ |
1718423058653380608 |