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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. 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.

Methods and Results: We assessed the impact of maternal SARS-CoV-2 on HBCs isolated from 24 term placentas (N = 10 SARS-CoV-2 positive cases, 14 negative controls). 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 (HBC-iMGs), with impaired synaptic pruning behavior compared to HBC models from negative controls.

Conclusion: These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.

Titel:	Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment.
Autor/in / Beteiligte Person:	Shook, LL ; Batorsky, RE ; De Guzman, RM ; McCrea, LT ; Brigida, SM ; Horng, JE ; Sheridan, SD ; Kholod, O ; Cook, AM ; Li, JZ ; Slonim, DK ; Goods, BA ; Perlis, RH ; Edlow, AG
Link:	Full Text Finder (Volltext)
Zeitschrift:	Journal of neuroinflammation, Jg. 21 (2024-06-25), Heft 1, S. 163
Veröffentlichung:	[London] : BioMed Central, c2004-, 2024
Medientyp:	academicJournal
ISSN:	1742-2094 (electronic)
DOI:	10.1186/s12974-024-03157-w
Schlagwort:	Female Pregnancy Humans Fetus Adult Brain virology Brain pathology Mice Animals Microglia virology Placenta virology COVID-19 immunology Macrophages virology Pregnancy Complications, Infectious virology Pregnancy Complications, Infectious pathology SARS-CoV-2 pathogenicity
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [J Neuroinflammation] 2024 Jun 25; Vol. 21 (1), pp. 163. <i>Date of Electronic Publication: </i>2024 Jun 25. MeSH Terms: Microglia* / virology ; Placenta* / virology ; COVID-19* / immunology ; Macrophages* / virology ; Pregnancy Complications, Infectious* / virology ; Pregnancy Complications, Infectious* / pathology ; SARS-CoV-2* / pathogenicity ; Female ; Pregnancy ; Humans ; Fetus ; Adult ; Brain / virology ; Brain / pathology ; Mice ; Animals References: Front Pharmacol. 2020 Jun 17;11:901. (PMID: 32625094) ; Cell Rep. 2022 Jun 14;39(11):110938. (PMID: 35662411) ; Brain Behav Immun. 2012 May;26(4):607-16. (PMID: 22310922) ; Anat Sci Int. 2022 Jan;97(1):1-14. (PMID: 34537900) ; JAMA Psychiatry. 2019 Jun 1;76(6):594-602. (PMID: 30840048) ; Nat Commun. 2022 Jan 18;13(1):320. (PMID: 35042863) ; Immunol Rev. 2022 Oct;311(1):205-223. 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(PMID: 22982217) Grant Information: 5K12HD103096 Eunice Kennedy Shriver National Institute of Child Health and Human Development; 1R01HD100022-01 Eunice Kennedy Shriver National Institute of Child Health and Human Development; 5T32HG010464 United States NH NIH HHS; P20GM130454 United States GM NIGMS NIH HHS; 1RF1MH132336-01 United States MH NIMH NIH HHS; 1RF1MH132336-01 United States MH NIMH NIH HHS Contributed Indexing: Keywords: COVID-19; Fetal brain; Hofbauer cells; Microglia; Neurodevelopment; Neuroimmune; Placenta; SARS-CoV-2; Single-cell RNA sequencing Entry Date(s): Date Created: 20240625 Date Completed: 20240626 Latest Revision: 20240628 Update Code: 20240628 PubMed Central ID: PMC11197235

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