Differential Transcriptomes and Methylomes of Trophoblast Stem Cells From Naturally-Fertilized and Somatic Cell Nuclear-Transferred Embryos

Trophoblast stem cells (TSCs) are essential for the development of mammals, as they provide the cells that form the placenta. These cells can be derived from trophoblast cells, but deriving them from somatic cell nuclear transfer (NT) blastocysts is not very efficient. This study profiles the transcriptomes across the stages of TSC derivation and found that treatment with fibroblast growth factor 4 (FGF4) resulted in many differentially expressed genes (DEGs) at outgrowth and initiated a transcription program for TSC formation. The study also examined DNA methylation dynamics, revealing a very low level before FGF4 treatment and gradual increases afterward. FGF4 treatment results in a distinct DNA methylation remodeling process committed to TSC formation.

• 1
  Seventy-five transcription factors (TFs) are continuously upregulated during NF TSC derivation, and their transcription profiles can infer the time course of NF, but not NT, TSC derivation.
• 2
  Most differentially expressed genes (DEGs) in NT outgrowth are rescued in SNT outgrowth, and the correct time course of SNT TSC derivation can be inferred accordingly.
• 3
  FGF4 treatment increases DNA methylation in outgrowth, directing progress to TSC formation, and specific highly methylated CpG islands (CGIs) in the outgrowth become aberrantly highly methylated (AHM) in NT and SNT TSCs.