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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...

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Autores principales: Odabasi, Yusuf Caglar, Yanasik, Sena, Saglam-Metiner, Pelin, Kaymaz, Yasin, Yesil-Celiktas, Ozlem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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.
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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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