Id-2 regulates critical aspects of human cytotrophoblast differentiation, invasion and migration

摘要: During early human placental development, the conceptus attaches itself to uterus through cytotrophoblast invasion. Invasive cells differentiate from precursor villous cytotrophoblasts, but essential regulating factors in this process are unknown. Basic helix-loop-helix (bHLH) transcription factor dimers regulators of mouse trophoblast development. We therefore examined importance family placenta. In many cell lineages, bHLH sequestered by members Id family, HLH proteins that lack basic DNA binding domain (Inhibitor (Id-1 Id-4)). differentiation some tissues, expression declines, allowing dimerize, bind and trans-activate lineage-specific genes. To begin study role we first characterized cells. The expressed Id-3 constitutively; Id-2 was downregulated, at mRNA protein levels, as differentiated culture situ, respectively. cases when compromised (in placentas women with preeclampsia, or grown under hypoxic conditions culture), maintained. assess functional relevance these correlations, used an adenovirus vector maintain cultured cytotrophoblasts. Compared control (lacZ-expressing) cells, cytotrophoblasts transduced constitutively express retained characteristics undifferentiated cells: (alpha)1 integrin low cyclin B retained. Furthermore, invasion Matrigel partially inhibited migration strikingly enhanced Id-2-expressing These results suggest it partners play important roles