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空间单细胞分析揭示了整个孕期胎盘绒毛的结构和免疫重塑。

Spatial single-cell analysis identifies placental villi structuraland immune remodeling across gestation.

作者信息

Velagala Suganthinie, Phan Long, Eke Chino, Fernandes Analie, Rice Tyler A, Olaloye Oluwabunmi, Konnikova Liza

机构信息

Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.

Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Program in Human and Translational Immunology, Yale School of Medicine, New Haven, CT, USA; Program in Translational Biomedicine, Yale School of Medicine, New Haven, CT, USA; Center for Systems and Engineering Immunology, Yale School of Medicine, New Haven, CT, USA.

出版信息

Mucosal Immunol. 2025 Aug;18(4):848-860. doi: 10.1016/j.mucimm.2025.04.005. Epub 2025 Apr 25.

DOI:10.1016/j.mucimm.2025.04.005
PMID:40288579
Abstract

Pregnancies rely upon the balance between fetal and maternal immune systems. Employing imaging mass cytometry, this study creates a spatial map landscape to unravel the cellular dynamics within the placental villi (PV). Consistent with previous data we report structural remodeling in PV, highlighted by increased syncytial trophoblasts, vascular smooth muscle cells, and endothelial cells in term PV. Additionally, we identified that rare immune populations including dendritic cells, innate lymphoid cells, and myeloid-derived suppressor cells in mid-gestation were more abundant and activated than in term placentas, suggesting a potentially tolerogenic state. Conversely, various macrophage subtypes were increased and in combination with rare T-cells exhibited heightened activation markers, possibly indicating increased signaling in preparation for parturition. In mid-gestation, fibroblasts had increased interactions with trophoblasts, while term samples exhibited close adjacencies between trophoblasts, vascular smooth muscle cells, and macrophages. This study offers insights into the PV cellular composition changes between mid and full-term samples, providing a foundation for future studies to understand the mechanisms of preterm birth and other pregnancy complications.

摘要

妊娠依赖于胎儿和母体免疫系统之间的平衡。本研究采用成像质谱流式细胞术,创建了一个空间图谱景观,以揭示胎盘绒毛(PV)内的细胞动态。与先前的数据一致,我们报告了PV中的结构重塑,足月PV中合体滋养层细胞、血管平滑肌细胞和内皮细胞的增加突出了这一点。此外,我们发现,妊娠中期包括树突状细胞、固有淋巴细胞和髓系来源的抑制细胞在内的稀有免疫群体比足月胎盘更为丰富且被激活,这表明存在潜在的免疫耐受状态。相反,各种巨噬细胞亚型增加,并且与稀有T细胞一起表现出更高的激活标志物,这可能表明为分娩做准备的信号增加。在妊娠中期,成纤维细胞与滋养层细胞的相互作用增加,而足月样本显示滋养层细胞、血管平滑肌细胞和巨噬细胞之间紧密相邻。本研究为了解中期和足月样本之间PV细胞组成的变化提供了见解,为未来研究早产和其他妊娠并发症的机制奠定了基础。

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