Distinct transcriptional and epigenomic programs define Hofbauer cells in term placenta
Benjámin R Baráth1,2,3, Dóra Bojcsuk1, Krisztian Bene1,3
1Department of Biochemistry and Molecular Biology, Faculty of Medicine, and.
JCI Insight
|December 23, 2025
Summary
Hofbauer cells (HBCs) in the placenta are distinct fetal macrophages. This study defines their unique transcriptomic and epigenomic profiles, revealing regulatory networks shaping their specialized functions in placental biology.
Area of Science:
- Reproductive biology
- Immunology
- Genomics
Background:
- Hofbauer cells (HBCs) are crucial fetal macrophages in the placenta.
- Their roles in placental development and function are recognized, but regulatory mechanisms remain unclear.
Purpose of the Study:
- To define the transcriptomic and epigenomic features of placental HBCs.
- To investigate HBC transcriptional responsiveness and phenotypic diversity.
Main Methods:
- Chromatin accessibility profiling (ATAC-seq) and bulk RNA sequencing.
- In vitro stimulation assays and mass cytometry analysis.
Main Results:
- HBCs possess unique gene expression and chromatin accessibility profiles distinct from other macrophages.
- A regulatory network involving nuclear receptors (NR4A1-3, GR) and RFX factors shapes HBC identity, impacting lipid metabolism and angiogenesis.
- HBCs showed increased transcriptional activity and CD36 induction upon IL-4 and RSG stimulation, displaying markers of both immature and mature states.
Conclusions:
- Hofbauer cells represent a distinct and diverse macrophage population within the human placenta.
- They possess specialized and adaptable regulatory programs for placental functions.
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