@article{efbf9d9c0cf749b2a70a5b447fa21858,
title = "Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood",
abstract = "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.",
author = "Powell, {Timothy R.} and Tytus Murphy and Lee, {Sang H.} and Duarte, {Rodrigo R. R.} and Lee, {Hyun Ah} and Demelza Smeeth and Jack Price and Gerome Breen and Sandrine Thuret",
note = "Funding Information: In vitro work and subsequent expression studies were primarily funded by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South. London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Thuret, Murphy and Price have also received funding support from Medical Research Council and Cohen Charitable Trust. Powell is funded by a Medical Research Council Skills Development Fellowship (MR/N014863/1) and has received research funding from Psychiatry Research Trust. Duarte is funded by a Science without Borders PhD scholarship (Brazil, CAPES BEX 1279-13-0). Smeeth{\textquoteright}s PhD studentship is sponsored by the Guy{\textquoteright}s and St Thomas{\textquoteright} Charity. Lee is in receipt of a King{\textquoteright}s College London Graduate School International Research PhD Studentship. We would also like to acknowledge the work of the ENIGMA Consortium, as we used genome-wide summary statistics from ENIGMA in order to perform genetic pathway analysis. Funding Information: Competing Interests: Price has received consultancy fees from the ReNeuron Group. Breen has received research funding from Eli Lilly. All other authors have declared that no competing interests exist. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41598-017-15042-z",
language = "English",
volume = "7",
pages = "1--10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}