Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity.
Rebecca BatorskyAlexis M CeasrineLydia L ShookSezen KislalEvan A BordtBenjamin A DevlinRoy H PerlisDonna K SlonimStaci D BilboAndrea G EdlowPublished in: bioRxiv : the preprint server for biology (2023)
Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs. Comparison with human datasets demonstrated conservation of placental resident macrophage signatures between mice and humans. Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders in the setting of maternal exposures.
Keyphrases
- single cell
- rna seq
- inflammatory response
- gene expression
- induced apoptosis
- neuropathic pain
- birth weight
- pregnancy outcomes
- metabolic syndrome
- insulin resistance
- high fat diet induced
- high throughput
- white matter
- resting state
- weight gain
- cell cycle arrest
- lipopolysaccharide induced
- weight loss
- lps induced
- mouse model
- type diabetes
- randomized controlled trial
- endoplasmic reticulum stress
- dna methylation
- stem cells
- public health
- endothelial cells
- pregnant women
- high fat diet
- functional connectivity
- spinal cord injury
- signaling pathway
- mesenchymal stem cells
- body mass index
- patient safety
- adipose tissue
- spinal cord
- skeletal muscle
- induced pluripotent stem cells
- cerebral ischemia
- physical activity
- bone marrow
- quality improvement
- air pollution