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
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