Abstract
The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA‐Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5. These findings provide avenues for further understanding of the mechanisms underlying mammalian placental syncytiotrophoblast development.
Highlights
The human placenta performs many of the diverse functions that control maternal metabolism relating to fetal growth and development that mediate the survival of the offspring
To determine the genes differentially expressed in the 6d C2C12 myotubes versus the 0d C2C12 myoblasts, we analyzed the 50 most upregulated genes in these two phenotypes
While the gene ontology terms that were significantly enriched in the genes we analyzed in BeWo cells included sex differentiation, reproduction, tissue development, and amino acid transport, in C2C12 cells the terms most enriched in the genes we analyzed involved, perhaps not surprisingly, muscle development and muscle contraction
Summary
The human placenta performs many of the diverse functions that control maternal metabolism relating to fetal growth and development that mediate the survival of the offspring. Perhaps the best-studied mammalian system of syncytia formation is that of myoblast fusion to form multi-nucleate myotubes and myofibers (Petrany & Millay, 2019; Schejter, 2016). Villous cytotrophoblasts isolated from human term placentas undergo differentiation and fusion into syncytia during culture (Azar et al, 2018; Kliman et al, 1986; Nelson et al, 1999). The murine C2C12 myoblast cell line undergoes triggered differentiation and regulated syncytia formation to myotubes in vitro (Petrany & Millay, 2019; Schejter, 2016). We exploit the power of these two cell models (BeWo, C2C12) to utilize an unbiased approach to identify genes, and their protein products, which are upregulated in the two mammalian cell systems that reflect cell-cell fusion and syncytia formation. We undertook this study with the expectation that common mechanisms or pathways would be found in myoblast fusion and cytotrophoblast fusion
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