title: Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant cells and defines multipotent progenitors in the developing placenta.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Arne
authors.initials: A
authors.lastname: Mould
authors.forename: Marc A J
authors.initials: MA
authors.lastname: Morgan
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Bikoff
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Robertson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000166:cytology*; D051379:Mice; D010920:Placenta / Q000098:blood supply / Q000166:cytology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology*
chemical_list: C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1