Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant cells and defines multipotent progenitors in the developing placenta

• Published in: Genes & development Vol. 26; no. 18; pp. 2063 - 2074
• Main Authors: Mould, Arne, Morgan, Marc A J, Li, Li, Bikoff, Elizabeth K, Robertson, Elizabeth J
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15-09-2012
• Subjects: Animals; Cell Differentiation; Female; Gene Expression Profiling; Gene Expression Regulation; Giant Cells - cytology; Mice; Placenta - blood supply; Placenta - cytology; Positive Regulatory Domain I-Binding Factor 1; Pregnancy; Research Paper; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Trophoblasts - cytology
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.199828.112

Developmental arrest of Blimp1/Prdm1 mutant embryos at around embryonic day 10.5 (E10.5) has been attributed to placental disturbances. Here we investigate Blimp1/Prdm1 requirements in the trophoblast cell lineage. Loss of function disrupts specification of the invasive spiral artery-associated trophoblast giant cells (SpA-TGCs) surrounding maternal blood vessels and severely compromises the ability of the spongiotrophoblast layer to expand appropriately, secondarily causing collapse of the underlying labyrinth layer. Additionally, we identify a population of proliferating Blimp1(+) diploid cells present within the spongiotrophoblast layer. Lineage tracing experiments exploiting a novel Prdm1.Cre-LacZ allele demonstrate that these Blimp1(+) cells give rise to the mature SpA-TGCs, canal TGCs, and glycogen trophoblasts. In sum, the transcriptional repressor Blimp1/Prdm1 is required for terminal differentiation of SpA-TGCs and defines a lineage-restricted progenitor cell population contributing to placental growth and morphogenesis.