Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Genes Dev. 2012 Sep 15;26(18):2063-74. 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.
胚胎发育至约 10.5 天（E10.5）时，Blimp1/Prdm1 突变体胚胎的发育停滞归因于胎盘紊乱。在这里，我们研究了 Blimp1/Prdm1 在滋养细胞谱系中的需求。功能丧失会破坏围绕母体血管的浸润性螺旋动脉相关滋养细胞巨细胞（SpA-TGC）的特化，并严重损害海绵滋养层适当扩张的能力，进而导致下面的绒毛层塌陷。此外，我们还鉴定出在海绵滋养层中存在一群增殖的 Blimp1(+)二倍体细胞。利用一种新型的 Prdm1.Cre-LacZ 等位基因进行的谱系追踪实验表明，这些 Blimp1(+)细胞分化为成熟的 SpA-TGC、管腔 TGC 和糖原滋养细胞。总之，转录抑制因子 Blimp1/Prdm1 是 SpA-TGC 终末分化所必需的，并定义了一个谱系限制的祖细胞群体，有助于胎盘的生长和形态发生。
