Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Batorsky, Rebecca; Ceasrine, Alexis M.; Shook, Lydia L.; Kislal, Sezen; Bordt, Evan A.; Devlin, Benjamin A.; Perlis, Roy H.; Slonim, Donna K.; Bilbo, Staci D.; Edlow, Andrea G.

doi:10.1101/2023.12.16.571680

Cited by 3 publications

(1 citation statement)

References 126 publications

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“…Excess maternal adiposity has been reported to alter the composition and function of maternal monocytes in peripheral blood, as well as macrophages found in placental and maternal adipose tissues during late gestation, toward a proinflammatory phenotype [ 33 , 47 ]. A recent study showed that Hofbauer cells and microglia share a similar developmental lineage and correlations in gene dysregulation were observed between the populations during maternal obesity [ 48 ]. This suggests that the readily abundant cells in the placenta provide insight into the developmental function of neonatal microglia.…”

Section: Impact Of Maternal Obesity/wsd On Maternal and Placental Imm...mentioning

confidence: 99%

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Nelson,

Friedman

2024

IJMS

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Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

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Section: Impact Of Maternal Obesity/wsd On Maternal and Placental Imm...mentioning

confidence: 99%

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Nelson,

Friedman

2024

IJMS

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From Noise to Knowledge: Diffusion Probabilistic Model-Based Neural Inference of Gene Regulatory Networks

Zhu,

Slonim

2023

Preprint

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Understanding gene regulatory networks (GRNs) is crucial for unraveling cellular mechanisms and enhancing therapeutic interventions. Original methods for GRN inference from bulk expression data often struggled with the high dimensionality and inherent noise in the data. The prevalence of dropout events and background noise inherent in single-cell RNA sequencing has only increased the challenges. Here we introduce RegDiffusion, a novel neural network structure inspired by Denoising Diffusion Probabilistic Models but focusing on the regulatory effects among feature variables. Unlike other GRN methods for single-cell RNA-sequencing data, RegDiffusion introduces Gaussian noise to the input data following a diffusion schedule. It is subsequently trained to predict the added noise using a neural network with a parameterized adjacency matrix. We show that using this process, GRNs can be effectively learned with a surprisingly simple model architecture. In our benchmark experiments, RegDiffusion demonstrates superior performance compared to several baseline methods on multiple datasets. This work not only introduces a fresh perspective on GRN inference but also highlights the promising capacity of diffusion-based models in the area of single-cell analysis. The RegDiffusion software is available athttps://github.com/TuftsBCB/RegDiffusion.

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Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

Shook,

Batorsky,

De Guzman

et al. 2023

Preprint

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The SARS-CoV-2 virus activates maternal and placental immune responses, which in the setting of other infections occurring during pregnancy are known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. Here, we assessed the impact of maternal SARS-CoV-2 on HBCs isolated from term placentas using single-cell RNA-sequencing. We demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells, with altered morphology and impaired synaptic pruning behavior compared to HBC models from negative controls. These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.

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Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Cited by 3 publications

References 126 publications

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

From Noise to Knowledge: Diffusion Probabilistic Model-Based Neural Inference of Gene Regulatory Networks

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

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