4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-16603-z

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Funding

  1. Wellcome Trust [214175/Z/18/Z, 107457, 203141/Z/16/Z]
  2. NIH/NICHD [R01HD042311]
  3. Wellcome Trust [214175/Z/18/Z] Funding Source: Wellcome Trust

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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 IFN gamma 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. The transcriptional repressor Blimp1/PRDM1 regulates cell fate decisions in the developing embryo and adult tissues. Here the authors show that conditional inactivation within maternal uterine tissues results in a defective primary decidual zone barrier, increased expression of inflammatory cytokines IFN gamma and Csf1, and early embryonic lethality during pregnancy.

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