Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment DOI Open Access
Lydia L. Shook, Rebecca Batorsky, Rose M. De Guzman

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 30, 2023

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

Language: Английский

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment DOI Creative Commons
Lydia L. Shook, Rebecca Batorsky, Rose M. De Guzman

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 25, 2024

Abstract Background The SARS-CoV-2 virus activates maternal and placental immune responses. Such activation in the setting of other infections during pregnancy is known to impact fetal brain development. effects on neurodevelopment are mediated at least part by microglia. However, microglia inaccessible for direct analysis, there no validated non-invasive surrogate models evaluate utero microglial priming function. We have previously demonstrated shared transcriptional programs between Hofbauer cells (HBCs, or macrophages) mouse models. Methods results assessed HBCs isolated from 24 term placentas ( N = 10 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we that HBC subpopulations exhibit distinct cellular programs, with specific differentially impacted SARS-CoV-2. Assessment expressed genes implied impaired phagocytosis, a key function both microglia, some subclusters. Leveraging synaptic pruning, showed pregnancies can be transdifferentiated into microglia-like (HBC-iMGs), pruning behavior compared controls. Conclusion These findings suggest birth used create personalized offspring programming.

Language: Английский

Citations

6
Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment DOI Open Access
Lydia L. Shook, Rebecca Batorsky, Rose M. De Guzman

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 30, 2023

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

Language: Английский

Citations

2