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| Status |
Public on Nov 29, 2022 |
| Title |
Serotonin-1A receptor, a psychiatric disease risk factor, modulates offspring immunity via sex-dependent genetic nurture |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Peripheral whole blood (n = 4 females) or the placenta decidua (n = 3 females) was collected from pregnant female mice (Swiss Webster wild type and 5HT1A-R +/- heterozygotes) at GD10.5 and pooled for single cell or single nucleus sequencing, respectively.
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| Contributor(s) |
Chen RJ, Nabila A, Toth M |
| Citation(s) |
36458257 |
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| Submission date |
Nov 02, 2022 |
| Last update date |
Jan 03, 2023 |
| Contact name |
Miklos Toth |
| Organization name |
Weill Cornell Medicine
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| Street address |
525 E. 68th St Whitney Pavilion Floor 5
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| City |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA896913 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE217086_RAW.tar |
585.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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