Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease
Purpose The purpose of this study was to analyze the transcriptomic changes in the striatum of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and uncover its association with the methyl-CpG binding protein 2 (MeCP2) mediated-changes in striatal epigenetic signature during Alzheimer...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Korean Continence Society
2022-11-01
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| Series: | International Neurourology Journal |
| Subjects: | |
| Online Access: | http://einj.org/upload/pdf/inj-2244256-128.pdf |
| _version_ | 1798014522680672256 |
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| author | Tae Kyoo Kim Sangjoon Lee Heh-In Im |
| author_facet | Tae Kyoo Kim Sangjoon Lee Heh-In Im |
| author_sort | Tae Kyoo Kim |
| collection | DOAJ |
| description | Purpose The purpose of this study was to analyze the transcriptomic changes in the striatum of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and uncover its association with the methyl-CpG binding protein 2 (MeCP2) mediated-changes in striatal epigenetic signature during Alzheimer disease (AD) pathological progression. Methods To observe transcriptomic alterations in the striatum before the onset of cognitive impairment in APP/PS1 mice, quantitative 3’mRNA sequencing was performed with RNA extracted from the striatum of 6-month-old and 12-month-old wildtype and APP/PS1 mice. In addition, chromatin immunoprecipitation sequencing was conducted with the DNA from wildtype and APP/PS1 mice of the same age as aforementioned. For transcriptomic analysis, comparison terms were constructed based on aging and transgene expression—normal-aging (12-month-old wildtype/6-month-old wildtype), early-AD (6-month-old APP/PS1/6-month-old wildtype), and late-AD (12-month-old APP/PS1/6-month-old wildtype). To compare the changes in biological pathways and networks, we analyzed gene lists from each comparison term via bioinformatics tools including DAVID (Database for Annotation, Visualization, and Integrated Discovery), STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), and SynGO (Synaptic Gene Ontologies). Furthermore, to assume the effect MeCP2 in AD pathological conditions may have on the transcriptome regulation, analysis of the common genes from Quant-Seq and MeCP2-ChIP-Seq was performed. Results Enriched pathways including immune system and inflammatory response were confirmed in normal- aging and lateAD, respectively. In particular, enriched pathways of gene expression regulation, transcriptional regulation, and protein catabolic pathways were found to be significantly altered in early-AD. MeCP2-bound genes that were significantly altered in the transcriptome were suggested to be target genes that have a role in the striatum of the early-stage AD model. Conclusions This study confirmed that the alteration of the striatal transcriptomic profile in APP/PS1 mice was involved with several biological pathways. Additionally, comparative analysis of the transcriptomic changes and the MeCP2 bound regions found that a group of differentially expressed genes may be regulated under the epigenetic control of MeCP2. |
| first_indexed | 2024-04-11T15:18:38Z |
| format | Article |
| id | doaj.art-e494e41c67fc460d88feee4cf420f7d1 |
| institution | Directory Open Access Journal |
| issn | 2093-4777 2093-6931 |
| language | English |
| last_indexed | 2024-04-11T15:18:38Z |
| publishDate | 2022-11-01 |
| publisher | Korean Continence Society |
| record_format | Article |
| series | International Neurourology Journal |
| spelling | doaj.art-e494e41c67fc460d88feee4cf420f7d12022-12-22T04:16:25ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312022-11-0126Suppl 2S11712510.5213/inj.2244256.1281021Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer DiseaseTae Kyoo Kim0Sangjoon Lee1Heh-In Im2 Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, KoreaPurpose The purpose of this study was to analyze the transcriptomic changes in the striatum of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and uncover its association with the methyl-CpG binding protein 2 (MeCP2) mediated-changes in striatal epigenetic signature during Alzheimer disease (AD) pathological progression. Methods To observe transcriptomic alterations in the striatum before the onset of cognitive impairment in APP/PS1 mice, quantitative 3’mRNA sequencing was performed with RNA extracted from the striatum of 6-month-old and 12-month-old wildtype and APP/PS1 mice. In addition, chromatin immunoprecipitation sequencing was conducted with the DNA from wildtype and APP/PS1 mice of the same age as aforementioned. For transcriptomic analysis, comparison terms were constructed based on aging and transgene expression—normal-aging (12-month-old wildtype/6-month-old wildtype), early-AD (6-month-old APP/PS1/6-month-old wildtype), and late-AD (12-month-old APP/PS1/6-month-old wildtype). To compare the changes in biological pathways and networks, we analyzed gene lists from each comparison term via bioinformatics tools including DAVID (Database for Annotation, Visualization, and Integrated Discovery), STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), and SynGO (Synaptic Gene Ontologies). Furthermore, to assume the effect MeCP2 in AD pathological conditions may have on the transcriptome regulation, analysis of the common genes from Quant-Seq and MeCP2-ChIP-Seq was performed. Results Enriched pathways including immune system and inflammatory response were confirmed in normal- aging and lateAD, respectively. In particular, enriched pathways of gene expression regulation, transcriptional regulation, and protein catabolic pathways were found to be significantly altered in early-AD. MeCP2-bound genes that were significantly altered in the transcriptome were suggested to be target genes that have a role in the striatum of the early-stage AD model. Conclusions This study confirmed that the alteration of the striatal transcriptomic profile in APP/PS1 mice was involved with several biological pathways. Additionally, comparative analysis of the transcriptomic changes and the MeCP2 bound regions found that a group of differentially expressed genes may be regulated under the epigenetic control of MeCP2.http://einj.org/upload/pdf/inj-2244256-128.pdfstriatumquant-seq 3’mrna sequencingalzheimer diseasechromatin immunoprecipitation sequencingmecp2 |
| spellingShingle | Tae Kyoo Kim Sangjoon Lee Heh-In Im Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease International Neurourology Journal striatum quant-seq 3’mrna sequencing alzheimer disease chromatin immunoprecipitation sequencing mecp2 |
| title | Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease |
| title_full | Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease |
| title_fullStr | Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease |
| title_full_unstemmed | Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease |
| title_short | Quantitative Sequencing Analysis of the Striatal Transcriptome in a Mouse Model of Alzheimer Disease |
| title_sort | quantitative sequencing analysis of the striatal transcriptome in a mouse model of alzheimer disease |
| topic | striatum quant-seq 3’mrna sequencing alzheimer disease chromatin immunoprecipitation sequencing mecp2 |
| url | http://einj.org/upload/pdf/inj-2244256-128.pdf |
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