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转录抑制因子 Blimp1/PRDM1 调控小鼠母体蜕膜反应。

The transcriptional repressor Blimp1/PRDM1 regulates the maternal decidual response in mice.

机构信息

Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.

Department of Human Biology, University of Cape Town, Cape Town, 7925, South Africa.

出版信息

Nat Commun. 2020 Jun 3;11(1):2782. doi: 10.1038/s41467-020-16603-z.

Abstract

The transcriptional repressor Blimp1 controls cell fate decisions in the developing embryo and adult tissues. Here we describe Blimp1 expression and functional requirements within maternal uterine tissues during pregnancy. Expression is robustly up-regulated at early post-implantation stages in the primary decidual zone (PDZ) surrounding the embryo. Conditional inactivation results in defective formation of the PDZ barrier and abnormal trophectoderm invasion. RNA-Seq analysis demonstrates down-regulated expression of genes involved in cell adhesion and markers of decidualisation. In contrast, genes controlling immune responses including IFNγ are up-regulated. ChIP-Seq experiments identify candidate targets unique to the decidua as well as those shared across diverse cell types including a highly conserved peak at the Csf-1 gene promoter. Interestingly Blimp1 inactivation results in up-regulated Csf1 expression and macrophage recruitment into maternal decidual tissues. These results identify Blimp1 as a critical regulator of tissue remodelling and maternal tolerance during early stages of pregnancy.

摘要

转录抑制因子 Blimp1 控制胚胎发育和成人组织中的细胞命运决定。在这里,我们描述了 Blimp1 在妊娠期间母体子宫组织中的表达和功能要求。在胚胎周围的主要蜕膜区 (PDZ) 的早期着床后阶段,表达水平显著上调。条件性失活导致 PDZ 屏障形成缺陷和滋养层细胞异常浸润。RNA-Seq 分析表明,参与细胞黏附的基因和蜕膜化标志物的表达下调。相比之下,控制免疫反应的基因,包括 IFNγ,上调。ChIP-Seq 实验鉴定了仅在蜕膜中特有的候选靶基因以及在包括 CSF-1 基因启动子在内的多种细胞类型中共享的候选靶基因。有趣的是,Blimp1 的失活导致 CSF1 表达上调和巨噬细胞募集到母体蜕膜组织中。这些结果表明 Blimp1 是妊娠早期组织重塑和母体耐受的关键调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fac2/7270082/0b8bd552edd8/41467_2020_16603_Fig1_HTML.jpg

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