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Reconstitution of the uterine immune milieu after transplantation (scRNA-seq)

ABSTRACT: Reconstitution of the uterine immune milieu after transplantation (scRNA-seq)

PROVIDER: PRJNA1073937 | ENA |

REPOSITORIES: ENA

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Reconstitution of the uterine immune milieu after transplantation (scRNA-seq)

Project description:Maintenance of tissue-specific immunity is important for immunological fitness, but its establishment have been difficult to assess in humans. Here, we investigated reconstitution of the human uterine immune system by studying women undergoing uterus solid organ transplantation (UTx) or hematopoietic stem cell transplantation (HSCT). Through single-cell identification based on SNPs and disparate HLA expression using single-cell RNA sequencing or high-parameter flow cytometry, donor vs recipient cell origin was determined, and features of these cells were studied. Endometrial immune cell reconstitution occurred after both UTx and HSCT, at the transcriptomic, phenotypic, and spatial level. This occurred despite tacrolimus-induced calcineurin-mediated NFAT pathway inhibition, which affected de novo induction of tissue-residency features in vitro. Intriguingly, after HSCT, immune cells of male origin could reconstitute the endometrium. Collectively, our results proved insights into tissue immune system persistence and reconstitution capabilities in an organ undergoing continuous regeneration.

2025-08-22 | GSE255202 | GEO

The role of smooth muscle cell-derived IL-18 in uterine immune milieu and fetoplacental growth

Project description:There is a close relationship between pregnancy and immune responses. For example, an anti-inflammatory state is essential for maintaining pregnancy by promoting maternal tolerance toward the semi-allogeneic fetus, whereas pro-inflammatory conditions are crucial for processes such as maternal tissue remodeling during embryo implantation and the induction of labor. Increasing evidence suggests that various cell types within the uteroplacental immune environment contribute to these immune responses, and immunological approaches have been employed to investigate the pathophysiology and potential treatments of pregnancy-related complications. Interleukin-18 (IL-18) is a unique cytokine with both pro-inflammatory and anti-inflammatory properties; however, its roles during pregnancy remain largely unclear. We have found that smooth muscle cells (SMCs) in the uterine myometrium are an important source of IL-18, and that the homeostatic production of IL-18 promotes fetal development by supporting maternal uterine remodeling and placental growth. To further investigate the effects of IL-18 on the uterine immune milieu, we established SMC-specific Il18 conditional knockout (cKO) mice and performed RNA sequencing of uterine immune cells.

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Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation

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Human uterine Natural Killer cells regulate differentiation of extravillous trophoblast early in pregnancy - scRNA-seq data

Project description:We used trophoblast organoids differentiating to extravillous trophoblast (EVT) to study the effects of key cytokines secreted by uterine Natural Killer (uNK) cells on EVT behaviour. Specifically, we exposed the organoids to four uNK-derived cytokines (CSF1, CSF2, XCL1, CCL5) and collected cells at different time points along the EVT differentiation pathway for scRNA-seq. We observe enhanced EVT differentiation in cytokine-treated organoids demonstrated by the increased proportion of late EVT subtypes and regulation of related pathways such as epithelial-mesenchymal transition. Moreover, uNK cytokines affect other processes important during early pregnancy including dampening of inflammatory and adaptive immune responses, regulation of blood flow, and placental access to nutrients.

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The role of smooth muscle cell-derived IL-18 in uterine immune milieu and fetoplacental growth

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Establishment of hematopoietic stem cell compartment after single cell transplantation tracked by FIT approach [scRNA-seq]

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Longâterm engraftment of primary bone marrow stroma promotes hematopoietic reconstitution after transplantation

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