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Transcriptomic profiling of dorsal root ganglia of transgenic sickle and control mouse models for studying genetic signatures of pain in sickle cell disease

ABSTRACT: We sequenced mRNA from the dorsal root ganglion (DRG) of transgenic mouse models of sickle cell disease (SCD) and their transgenic controls. Each genotype (strains) were divided into two age groups and each age groups were subjected to two treatment conditions (each simulating acute and chronic pain respectively). Each of these 8 groups had 6 male mice (except one group had 7 mice) resulting into a total of 49 samples. The goal of mRNA sequencing of these samples is to identify genetic signatures associated with transition from acute to chronic pain in SCD.

ORGANISM(S): Mus musculus

PROVIDER: GSE86418 | GEO | 2017/04/05

SECONDARY ACCESSION(S): PRJNA341718

REPOSITORIES: GEO

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Project description:Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.

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Transcriptomic profiling of dorsal root ganglia of transgenic sickle and control mouse models for studying genetic signatures of pain in sickle cell disease

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