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Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface
Published on: May 21, 2015
Single-cell profiling of the peripheral blood immune landscape during mid- and late-stage pregnancy
Fan Gao1, Xia Li2, Hongyan Wang2
1Gene Joint Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
We aimed to determine the peripheral blood mononuclear cell (PBMC) immune profiles of mid- and late-stage pregnant women to establish a foundation for studying pregnancy-related diseases. Peripheral blood samples were collected from three women each during mid- and late-stage pregnancy, and PBMCs were extracted for single-cell RNA sequencing (scRNA-seq). Peripheral blood samples were also collected for flow cytometry analysis to validate the analytical results. HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells significantly differed in quantitative ratio and gene transcript level between women at mid- and late-stage pregnancy. In late pregnancy, cell-to-cell communication was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," exhibited high XIST expression, a gene that may be involved in the regulation of immune-related gene transcription and translation, and insulin signaling pathway, during pregnancy. Monocytes exhibited significant proinflammatory and metabolic properties in mid- and late-stage pregnancy, respectively. Natural killer (NK) cells were mainly involved in T- and B-cell-mediated signaling pathways, and in T cell differentiation, in mid-pregnancy. Enhanced innate immunity of NK cells was observed. Moreover, NK cells expressed genes associated with diabetes-related pathways in late-stage pregnancy. To conclude, we present detailed changes in the immune response occurring in pregnant women from mid- to late-stage gestation, revealing significant differences in PBMC subtypes and molecular properties. These findings provide insights into the physiopathological mechanisms of chronic hepatitis B infection, systemic lupus erythematosus, and gestational diabetes mellitus underlying systemic immune responses during mid- and late-stage pregnancy.NEW & NOTEWORTHY There are significant differences in three subtypes of memory/effector T cells (HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells) between mid- and late pregnancy. In late pregnancy, intercellular interaction was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," may be involved in the regulation of immune-related gene transcription and translation with a strong female bias.
We aimed to determine the peripheral blood mononuclear cell (PBMC) immune profiles of mid- and late-stage pregnant women to establish a foundation for studying pregnancy-related diseases. Peripheral blood samples were collected from three women each during mid- and late-stage pregnancy, and PBMCs were extracted for single-cell RNA sequencing (scRNA-seq). Peripheral blood samples were also collected for flow cytometry analysis to validate the analytical results. HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells significantly differed in quantitative ratio and gene transcript level between women at mid- and late-stage pregnancy. In late pregnancy, cell-to-cell communication was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," exhibited high XIST expression, a gene that may be involved in the regulation of immune-related gene transcription and translation, and insulin signaling pathway, during pregnancy. Monocytes exhibited significant proinflammatory and metabolic properties in mid- and late-stage pregnancy, respectively. Natural killer (NK) cells were mainly involved in T- and B-cell-mediated signaling pathways, and in T cell differentiation, in mid-pregnancy. Enhanced innate immunity of NK cells was observed. Moreover, NK cells expressed genes associated with diabetes-related pathways in late-stage pregnancy. To conclude, we present detailed changes in the immune response occurring in pregnant women from mid- to late-stage gestation, revealing significant differences in PBMC subtypes and molecular properties. These findings provide insights into the physiopathological mechanisms of chronic hepatitis B infection, systemic lupus erythematosus, and gestational diabetes mellitus underlying systemic immune responses during mid- and late-stage pregnancy.NEW & NOTEWORTHY There are significant differences in three subtypes of memory/effector T cells (HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells) between mid- and late pregnancy. In late pregnancy, intercellular interaction was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," may be involved in the regulation of immune-related gene transcription and translation with a strong female bias.

