Sex-Specific Effects of Testosterone on the Sexually Dimorphic Transcriptome and Epigenome of Embryonic Neural Stem/Progenitor Cells
Autor: | Matthew S. Bramble, Hayk Barseghyan, Neerja Vashist, Steven D Klein, Lara Roach, Eric Vilain, Tuck Ngun, Valerie A. Arboleda, Ascia Eskin, Jason E. Gosschalk, Allen Lipson |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Reproductive health and childbirth Inbred C57BL Epigenesis Genetic Transcriptome Histones Mice 0302 clinical medicine Neural Stem Cells Testosterone Genetics Pediatric Microscopy Sex Characteristics Multidisciplinary Sex Chromosomes Acetylation Neural stem cell Histone DNA methylation Neurological Female Sequence Analysis Biotechnology 1.1 Normal biological development and functioning Biology Fluorescence Article 03 medical and health sciences Genetic Underpinning research Animals Cell Lineage Epigenetics Progenitor cell Embryonic Stem Cells Sequence Analysis RNA Human Genome Neurosciences Epigenome DNA Methylation Stem Cell Research Embryonic stem cell Estrogen Mice Inbred C57BL 030104 developmental biology Microscopy Fluorescence biology.protein RNA 030217 neurology & neurosurgery Epigenesis |
Zdroj: | Scientific Reports Scientific reports, vol 6, iss 1 |
ISSN: | 2045-2322 |
Popis: | The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic brain development, we identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. RNA-sequencing identified 103 transcripts that were differentially expressed between XX and XY eNSCs at baseline (FDR = 0.10). Treatment with testosterone-propionate (TP) reveals sex-specific gene expression changes, causing 2854 and 792 transcripts to become differentially expressed on XX and XY genetic backgrounds respectively. Within the TP responsive transcripts, there was enrichment for genes which function as epigenetic regulators that affect both histone modifications and DNA methylation patterning. We observed that TP caused a global decrease in 5-methylcytosine abundance in both sexes, a transmissible effect that was maintained in cellular progeny. Additionally, we determined that TP was associated with residue-specific alterations in acetylation of histone tails. These findings highlight an unknown component of androgen action on cells within the developmental CNS, and contribute to a novel mechanism of action by which early hormonal organization is initiated and maintained. |
Databáze: | OpenAIRE |
Externí odkaz: |