Serotonin-1A receptor, a psychiatric disease risk factor, modulates offspring immunity via sex-dependent genetic nurture
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ABSTRACT:
PROVIDER: PRJNA896913 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22141100.fastq.gz | Fastqsanger.gz | |||
| SRR22141101.fastq.gz | Fastqsanger.gz | |||
| SRR22141102.fastq.gz | Fastqsanger.gz | |||
| SRR22141091.fastq.gz | Fastqsanger.gz | |||
| SRR22141092.fastq.gz | Fastqsanger.gz |
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Project description:Serotonin-1A receptor (5HT1AR) is highly expressed in corticolimbic regions and its deficit has been associated with anxiety and depression. A similar reduction in 5HT1AR heterozygous knockout (Het) mice results in anxiety-like and increased stress-reactivity phenotypes. Here we describe immunological abnormalities in Het females, characterized by an activated state of innate and adaptive immune cells. Het males showed only limited immune dysregulation. Similar immune abnormalities were present in the genetically WT female (F1) but not in male offspring of Het mothers, indicating sex-specific immune system abnormalities that are unrelated to the individual’s receptor expression but instead dependent on the mother’s 5HT1AR deficit, known as a maternal genetic effect or “genetic nurture”. Studying the maternal-fetal interface by scRNA-seq revealed reduced immune cell invasion to the decidua and accelerated trophoblast migration that was normalized by term. Despite these phenotypes, 5HT1AR is not, or only minimally expressed in the immune system and placenta, raising the possibility of a central regulation of the immune system by highly expressed brain receptors. We conclude that 5HT1AR deficit, by altering the maternal immune system and midgestational in utero environment, leads to sex-biased outcomes, predominantly immune dysregulation in females and anxiety-like behavior in males.
2022-11-29 | GSE217086 | GEO
Project description:Serotonin-1A receptor (5HT1AR) is highly expressed in corticolimbic regions and its deficit is associated with anxiety and depression. A similar reduction in 5HT1AR heterozygous knockout (Het) mice results in anxiety-like and increased stress-reactivity phenotypes. Here we describe immunological abnormalities in Het females, characterized by an activated state of innate and adaptive immune cells. Het males showed only limited immune dysregulation. Similar immune abnormalities were present in the genetically WT female (F1) but not male offspring of Het mothers, indicating sex-specific immune system abnormalities that are dependent on the mother's 5HT1AR deficit, known as maternal genetic effect or "genetic nurture". Expression profiling of the maternal-fetal interface revealed reduced immune cell invasion to decidua and accelerated trophoblast migration. These data suggest that 5HT1AR deficit, by altering the maternal immune system and midgestational in utero environment, leads to sex-biased outcomes, predominantly immune dysregulation in the female and anxiety-like behavior in the male offspring.
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Project description:Paternal stress can be encoded into altered epigenetic information to influence their offspring. How environment-induced perturbation in sperm epigenome is reprogrammed to protect offspring is less well understood. In the nematode Caenorhabditis elegans, parental Argonaute and small RNA pathway defend offspring against viruses, starvation, and pathogenic bacteria. Here we report that, when challenged by universal heat-shock stress, paternal Argonaute CSR-1A potentiates recovery of spermic H3K9me3 to secure the late somatic developmental competence of offspring. CSR-1A employs its repetitive RG motif to engage with SET-25/32, putative histone 3 lysine 9 (H3K9) methyltransferases, and helps germ cell to rescue suppressive chromatin marks H3K9me3 following stress, protecting the late development of somatic cells in the progeny. Finally, among the genes regulated by CSR-1A, we identified dim-1, at which decreased H3K9me3 persists in the progeny, and RNAi of dim-1 mitigates the somatic defects associated with csr-1a loss under stress. Thus, CSR-1A coordinates the epigenetic machinery to shield the latter stages of a progeny's development from the influences of the paternal environment. We speculate that, driven by both natural environmental stressors and the unique characteristics of spermatogenic chromatin, the emergence of multiple RG motif-featured and spermatogenesis-specific CSR-1A and small RNA serves as an adaptive strategy to safeguard against variability in the orchestration of inherited developmental programs from the paternal lineage.
2025-02-07 | GSE262243 | GEO
Project description:Paternal stress can be encoded into altered epigenetic information to influence their offspring. How environment-induced perturbation in sperm epigenome is reprogrammed to protect offspring is less well understood. In the nematode Caenorhabditis elegans, parental Argonaute and small RNA pathway defend offspring against viruses, starvation, and pathogenic bacteria. Here we report that, when challenged by universal heat-shock stress, paternal Argonaute CSR-1A potentiates recovery of spermic H3K9me3 to secure the late somatic developmental competence of offspring. CSR-1A employs its repetitive RG motif to engage with SET-25/32, putative histone 3 lysine 9 (H3K9) methyltransferases, and helps germ cell to rescue suppressive chromatin marks H3K9me3 following stress, protecting the late development of somatic cells in the progeny. Finally, among the genes regulated by CSR-1A, we identified dim-1, at which decreased H3K9me3 persists in the progeny, and RNAi of dim-1 mitigates the somatic defects associated with csr-1a loss under stress. Thus, CSR-1A coordinates the epigenetic machinery to shield the latter stages of a progeny's development from the influences of the paternal environment. We speculate that, driven by both natural environmental stressors and the unique characteristics of spermatogenic chromatin, the emergence of multiple RG motif-featured and spermatogenesis-specific CSR-1A and small RNA serves as an adaptive strategy to safeguard against variability in the orchestration of inherited developmental programs from the paternal lineage.
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Project description:Assessing the risks of long-term exposure to low doses of pharmaceuticals is an identified research need, particularly for those that may act as neural disruptors in non-vertebrate species. Selective serotonin reuptake inhibitors (SSRIs) act by blocking the re-uptake of serotonin in the nerve synapses, increasing the effective concentration of serotonin in the intra-synaptic space and therefore stimulating serotoninergic neurons. This effect is used worldwide to treat clinical depression in humans, with the consequence of their widespread release into the environment. SSRIs have been found to alter the reproductive physiology of D. magna and other invertebrates in a biphasic way. Low levels of fluoxetine stimulated offspring production in Daphnia magna and Ceriodaphnia dubia at 36 and 50 µg/l, respectively, but higher exposure levels inhibited reproduction in the same species. In this study we explore the hypothesis that SSRI can affect D. magna juvenile developmental rates and offspring production disrupting serotonin activity that is known to regulate carbohydrate and oxidative metabolic pathways. The primary mode of action was tested using transcriptomic analyses of juveniles and adults exposed to SSRIs (fluoxetine 80 ppbs, fluovoxamine 30 ppbs) and serotonin-immunocytochemistry assays of D. magna brains. Reproduction, respirometry and biochemical measurements allowed to related gene and immunological base effects to phenotypic responses.
2013-03-15 | E-GEOD-45053 | biostudies-arrayexpress
Project description:Argonaute CSR-1A promotes H3K9me3 maintenance to protect somatic development in offspring
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Project description:Argonaute CSR-1A promotes H3K9me3 maintenance to protect somatic development in offspring
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Project description:Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in which 5-HT can be added to histone proteins to regulate transcription, a process called H3 serotonylation. Here, we show that H3 serotonylation undergoes dynamic regulation during placental development, corresponding to gene expression changes that are known to influence key metabolic processes. Using transgenic mice, we demonstrate that placental H3 serotonylation largely depends on 5-HT uptake by the serotonin transporter (Sert/Slc6a4). Sert deletion robustly reduces enrichment of H3 serotonylation across the placental genome, and disrupts neurodevelopmental gene networks in offspring brain tissues. Thus, these findings suggest a novel role for H3 serotonylation in coordinating placental transcription at the intersection of maternal physiology and offspring brain development.
2024-01-23 | GSE246539 | GEO
Project description:Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in which 5-HT can be added to histone proteins to regulate transcription, a process called H3 serotonylation. Here, we show that H3 serotonylation undergoes dynamic regulation during placental development, corresponding to gene expression changes that are known to influence key metabolic processes. Using transgenic mice, we demonstrate that placental H3 serotonylation largely depends on 5-HT uptake by the serotonin transporter (Sert/Slc6a4). Sert deletion robustly reduces enrichment of H3 serotonylation across the placental genome, and disrupts neurodevelopmental gene networks in offspring brain tissues. Thus, these findings suggest a novel role for H3 serotonylation in coordinating placental transcription at the intersection of maternal physiology and offspring brain development.
2024-01-23 | GSE246538 | GEO