RNA-Seq identifies genes whose proteins are transformative in the differentiation of cytotrophoblast to syncytiotrophoblast, in human primary villous and BeWo trophoblasts

Christopher Azar,Alan L Schwartz,D Michael Nelson,Mark Valentine,Todd Druley,Julie Trausch-Azar

doi:10.1038/s41598-018-23379-2

Christopher Azar, Alan L Schwartz + Show 4 more

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https://doi.org/10.1038/s41598-018-23379-2

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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 and quantitative protein expression, we identified genes and their cognate proteins which are coordinately up- or down-regulated in two cellular models of cytotrophoblast to syncytiotrophoblast development, human primary villous and human BeWo cytotrophoblasts. These include hCGβ, TREML2, PAM, CRIP2, INHA, FLRG, SERPINF1, C17orf96, KRT17 and SAA1. These findings provide avenues for further understanding the mechanisms underlying mammalian placental synctiotrophoblast development.

Highlights

The mammalian placenta is a specialized organ that serves essential roles in fetal growth and development throughout pregnancy including regulated delivery of nutrients to the fetus and elimination of metabolic wastes, regulated gas exchange and secretion of hormones that maintain pregnancy
The processes that regulate villous cytotrophoblast fusion with syncytiotrophoblast are largely unknown, but pathways to multinucleated syncytia are better understood in myoblast cell-cell fusion[2]
Mediators identified to associate with cytotrophoblast fusion include syncytin-1, syncytin-2, SLC1A5, MFSD2A, galectin-1, transglutaminase 2-dependent deamidation of G3PD, and intermediate conductance Ca2+ activated channels[8,9,10,11,12,13,14]

Summary

Introduction

The mammalian placenta is a specialized organ that serves essential roles in fetal growth and development throughout pregnancy including regulated delivery of nutrients to the fetus and elimination of metabolic wastes, regulated gas exchange and secretion of hormones that maintain pregnancy. Mediators identified to associate with cytotrophoblast fusion include syncytin-1, syncytin-2, SLC1A5, MFSD2A, galectin-1, transglutaminase 2-dependent deamidation of G3PD, and intermediate conductance Ca2+ activated channels[8,9,10,11,12,13,14]. Best studied among these are syncytin-1 and syncytin-2, which are fusogenic Env glycoproteins of human endogenous retroviral origin. We exploit the power of these two cell models to undertake an unbiased approach to identify genes, and gene products, which are coordinately regulated, either both up or both down, in the two cell systems that reflect human cytotrophoblast fusion to syncytiotrophoblast

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