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Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease

Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of...

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Autores principales: Fedoseyeva, Viya B., Novosadova, Ekaterina V., Nenasheva, Valentina V., Novosadova, Lyudmila V., Grivennikov, Igor A., Tarantul, Vyacheslav Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299083/
https://www.ncbi.nlm.nih.gov/pubmed/37367477
http://dx.doi.org/10.3390/jdb11020023
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author Fedoseyeva, Viya B.
Novosadova, Ekaterina V.
Nenasheva, Valentina V.
Novosadova, Lyudmila V.
Grivennikov, Igor A.
Tarantul, Vyacheslav Z.
author_facet Fedoseyeva, Viya B.
Novosadova, Ekaterina V.
Nenasheva, Valentina V.
Novosadova, Lyudmila V.
Grivennikov, Igor A.
Tarantul, Vyacheslav Z.
author_sort Fedoseyeva, Viya B.
collection PubMed
description Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in PARK2 published previously. The high level of transcription of HOX family protein-coding genes and lncRNA transcribed from the HOX clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The HOX paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the HOX gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis.
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spelling pubmed-102990832023-06-28 Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease Fedoseyeva, Viya B. Novosadova, Ekaterina V. Nenasheva, Valentina V. Novosadova, Lyudmila V. Grivennikov, Igor A. Tarantul, Vyacheslav Z. J Dev Biol Article Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in PARK2 published previously. The high level of transcription of HOX family protein-coding genes and lncRNA transcribed from the HOX clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The HOX paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the HOX gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis. MDPI 2023-05-25 /pmc/articles/PMC10299083/ /pubmed/37367477 http://dx.doi.org/10.3390/jdb11020023 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fedoseyeva, Viya B.
Novosadova, Ekaterina V.
Nenasheva, Valentina V.
Novosadova, Lyudmila V.
Grivennikov, Igor A.
Tarantul, Vyacheslav Z.
Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
title Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
title_full Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
title_fullStr Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
title_full_unstemmed Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
title_short Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
title_sort transcription of hox genes is significantly increased during neuronal differentiation of ipscs derived from patients with parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299083/
https://www.ncbi.nlm.nih.gov/pubmed/37367477
http://dx.doi.org/10.3390/jdb11020023
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