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Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood

Hippocampal volumes are smaller in psychiatric disorder patients and lower levels of hippocampal neurogenesis are the hypothesized cause. Understanding which molecular processes regulate hippocampal progenitor differentiation might aid in the identification of novel drug targets that can promote lar...

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Autores principales: Powell, Timothy R., Murphy, Tytus, Lee, Sang H., Duarte, Rodrigo R. R., Lee, Hyun Ah, Smeeth, Demelza, Price, Jack, Breen, Gerome, Thuret, Sandrine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678432/
https://www.ncbi.nlm.nih.gov/pubmed/29118430
http://dx.doi.org/10.1038/s41598-017-15042-z
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author Powell, Timothy R.
Murphy, Tytus
Lee, Sang H.
Duarte, Rodrigo R. R.
Lee, Hyun Ah
Smeeth, Demelza
Price, Jack
Breen, Gerome
Thuret, Sandrine
author_facet Powell, Timothy R.
Murphy, Tytus
Lee, Sang H.
Duarte, Rodrigo R. R.
Lee, Hyun Ah
Smeeth, Demelza
Price, Jack
Breen, Gerome
Thuret, Sandrine
author_sort Powell, Timothy R.
collection PubMed
description Hippocampal volumes are smaller in psychiatric disorder patients and lower levels of hippocampal neurogenesis are the hypothesized cause. Understanding which molecular processes regulate hippocampal progenitor differentiation might aid in the identification of novel drug targets that can promote larger hippocampal volumes. Here we use a unique human cell line to assay genome-wide expression changes when hippocampal progenitor cells differentiate. RNA was extracted from proliferating cells versus differentiated neural cells and applied to Illumina Human HT-12 v4 Expression BeadChips. Linear regressions were used to determine the effect of differentiation on probe expression and we assessed enrichment for gene ontology (GO) terms. Genetic pathway analysis (MAGMA) was used to evaluate the relationship between hippocampal progenitor cell differentiation and adult hippocampal volume, using results from the imaging genomics consortium, ENIGMA. Downregulated transcripts were enriched for mitotic processes and upregulated transcripts were enriched for cell differentiation. Upregulated (differentiation) transcripts specifically, were also predictive of adult hippocampal volume; with Early growth response protein 2 identified as a hub transcription factor within the top GO term, and a potential drug target. Our results suggest that genes governing differentiation, rather than mitosis, have an impact on adult hippocampal volume and that these genes represent important drug targets.
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spelling pubmed-56784322017-11-17 Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood Powell, Timothy R. Murphy, Tytus Lee, Sang H. Duarte, Rodrigo R. R. Lee, Hyun Ah Smeeth, Demelza Price, Jack Breen, Gerome Thuret, Sandrine Sci Rep Article Hippocampal volumes are smaller in psychiatric disorder patients and lower levels of hippocampal neurogenesis are the hypothesized cause. Understanding which molecular processes regulate hippocampal progenitor differentiation might aid in the identification of novel drug targets that can promote larger hippocampal volumes. Here we use a unique human cell line to assay genome-wide expression changes when hippocampal progenitor cells differentiate. RNA was extracted from proliferating cells versus differentiated neural cells and applied to Illumina Human HT-12 v4 Expression BeadChips. Linear regressions were used to determine the effect of differentiation on probe expression and we assessed enrichment for gene ontology (GO) terms. Genetic pathway analysis (MAGMA) was used to evaluate the relationship between hippocampal progenitor cell differentiation and adult hippocampal volume, using results from the imaging genomics consortium, ENIGMA. Downregulated transcripts were enriched for mitotic processes and upregulated transcripts were enriched for cell differentiation. Upregulated (differentiation) transcripts specifically, were also predictive of adult hippocampal volume; with Early growth response protein 2 identified as a hub transcription factor within the top GO term, and a potential drug target. Our results suggest that genes governing differentiation, rather than mitosis, have an impact on adult hippocampal volume and that these genes represent important drug targets. Nature Publishing Group UK 2017-11-08 /pmc/articles/PMC5678432/ /pubmed/29118430 http://dx.doi.org/10.1038/s41598-017-15042-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Powell, Timothy R.
Murphy, Tytus
Lee, Sang H.
Duarte, Rodrigo R. R.
Lee, Hyun Ah
Smeeth, Demelza
Price, Jack
Breen, Gerome
Thuret, Sandrine
Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
title Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
title_full Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
title_fullStr Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
title_full_unstemmed Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
title_short Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
title_sort inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678432/
https://www.ncbi.nlm.nih.gov/pubmed/29118430
http://dx.doi.org/10.1038/s41598-017-15042-z
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