The transcriptional repressor Blimp1/PRDM1 regulates the maternal decidual response in mice.
Mubeen GoolamMaria-Eleni XypolitaIta CostelloJohn P LydonFrancesco J DeMayoElizabeth K BikoffElizabeth J RobertsonArne W MouldPublished in: Nature communications (2020)
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.
Keyphrases
- transcription factor
- pregnancy outcomes
- rna seq
- poor prognosis
- single cell
- gene expression
- immune response
- birth weight
- genome wide
- cell fate
- dna methylation
- pregnant women
- magnetic resonance imaging
- computed tomography
- high throughput
- long non coding rna
- bone marrow
- copy number
- mesenchymal stem cells
- body mass index
- cell migration
- gestational age
- weight gain
- insulin resistance
- physical activity
- heat stress
- heat shock
- childhood cancer
- preterm birth
- genome wide analysis