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Comprehensive Transcriptomic Investigation of Rett Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent Stem Cells to Neurons with Implications for Enriched Pathways
[Image: see text] Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder that has no cure apart from symptomatic treatments. While intense research efforts are required to fulfill this unmet need, the fundamental challenge is to obtain sufficient patient data. In this study, we used human...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666228/ https://www.ncbi.nlm.nih.gov/pubmed/38027357 http://dx.doi.org/10.1021/acsomega.3c06448 |
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author | Odabasi, Yusuf Caglar Yanasik, Sena Saglam-Metiner, Pelin Kaymaz, Yasin Yesil-Celiktas, Ozlem |
author_facet | Odabasi, Yusuf Caglar Yanasik, Sena Saglam-Metiner, Pelin Kaymaz, Yasin Yesil-Celiktas, Ozlem |
author_sort | Odabasi, Yusuf Caglar |
collection | PubMed |
description | [Image: see text] Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder that has no cure apart from symptomatic treatments. While intense research efforts are required to fulfill this unmet need, the fundamental challenge is to obtain sufficient patient data. In this study, we used human transcriptomic data of four different sample types from RTT patients including induced pluripotent stem cells, differentiated neural progenitor cells, differentiated neurons, and postmortem brain tissues with an increasing in vivo-like complexity to unveil specific trends in gene expressions across the samples. Based on DEG analysis, we identified F8A3, CNTN6, RPE65, and COL19A1 to have differential expression levels in three sample types and also observed previously reported genes such as MECP2, FOXG1, CACNA1G, SATB2, GABBR2, MEF2C, KCNJ10, and CUX2 in our study. Considering the significantly enriched pathways for each sample type, we observed a consistent increase in numbers from iPSCs to NEUs where MECP2 displayed profound effects. We also validated our GSEA results by using single-cell RNA-seq data. In WGCNA, we elicited a connection among MECP2, TNRC6A, and HOXA5. Our findings highlight the utility of transcriptomic analyses to determine genes that might lead to therapeutic strategies. |
format | Online Article Text |
id | pubmed-10666228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-106662282023-11-08 Comprehensive Transcriptomic Investigation of Rett Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent Stem Cells to Neurons with Implications for Enriched Pathways Odabasi, Yusuf Caglar Yanasik, Sena Saglam-Metiner, Pelin Kaymaz, Yasin Yesil-Celiktas, Ozlem ACS Omega [Image: see text] Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder that has no cure apart from symptomatic treatments. While intense research efforts are required to fulfill this unmet need, the fundamental challenge is to obtain sufficient patient data. In this study, we used human transcriptomic data of four different sample types from RTT patients including induced pluripotent stem cells, differentiated neural progenitor cells, differentiated neurons, and postmortem brain tissues with an increasing in vivo-like complexity to unveil specific trends in gene expressions across the samples. Based on DEG analysis, we identified F8A3, CNTN6, RPE65, and COL19A1 to have differential expression levels in three sample types and also observed previously reported genes such as MECP2, FOXG1, CACNA1G, SATB2, GABBR2, MEF2C, KCNJ10, and CUX2 in our study. Considering the significantly enriched pathways for each sample type, we observed a consistent increase in numbers from iPSCs to NEUs where MECP2 displayed profound effects. We also validated our GSEA results by using single-cell RNA-seq data. In WGCNA, we elicited a connection among MECP2, TNRC6A, and HOXA5. Our findings highlight the utility of transcriptomic analyses to determine genes that might lead to therapeutic strategies. American Chemical Society 2023-11-08 /pmc/articles/PMC10666228/ /pubmed/38027357 http://dx.doi.org/10.1021/acsomega.3c06448 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Odabasi, Yusuf Caglar Yanasik, Sena Saglam-Metiner, Pelin Kaymaz, Yasin Yesil-Celiktas, Ozlem Comprehensive Transcriptomic Investigation of Rett Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent Stem Cells to Neurons with Implications for Enriched Pathways |
title | Comprehensive Transcriptomic Investigation of Rett
Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent
Stem Cells to Neurons with Implications for Enriched Pathways |
title_full | Comprehensive Transcriptomic Investigation of Rett
Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent
Stem Cells to Neurons with Implications for Enriched Pathways |
title_fullStr | Comprehensive Transcriptomic Investigation of Rett
Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent
Stem Cells to Neurons with Implications for Enriched Pathways |
title_full_unstemmed | Comprehensive Transcriptomic Investigation of Rett
Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent
Stem Cells to Neurons with Implications for Enriched Pathways |
title_short | Comprehensive Transcriptomic Investigation of Rett
Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent
Stem Cells to Neurons with Implications for Enriched Pathways |
title_sort | comprehensive transcriptomic investigation of rett
syndrome reveals increasing complexity trends from induced pluripotent
stem cells to neurons with implications for enriched pathways |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666228/ https://www.ncbi.nlm.nih.gov/pubmed/38027357 http://dx.doi.org/10.1021/acsomega.3c06448 |
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