Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts

Stem Cell Res. 2021 Oct:56:102507. doi: 10.1016/j.scr.2021.102507. Epub 2021 Aug 19.

Abstract

Human trophoblast stem cells (hTSC) can be isolated from first trimester placenta but not from term placenta. Here we demonstrate that villous cytotrophoblasts (vCTB) from term placenta can be reprogrammed into induced trophoblastic stem-like cells (iTSC) by introducing sets of transcription factors. The iTSCs express TSC markers such as GATA3, TEAD4 and ELF5, and are multipotent, validated by their differentiation into both extravillous trophoblasts (EVT) and syncytiotrophoblasts (STB) in vitro and in vivo. The iTSC can be passaged indefinitely in vitro without slowing of growth. The transcriptome profile of these cells closely resembles the profile of hTSC isolated from first trimester placentae but different from the term placental vCTB from which they originated. The ability to reprogram cells from term placenta into iTSC will allow study of early gestation events which impact placental function later in gestation, including preeclampsia and spontaneous preterm birth.

Keywords: Differentiation; Placenta; Reprogramming; Stem cell; Trophoblast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation
  • DNA-Binding Proteins
  • Female
  • Humans
  • Infant, Newborn
  • Muscle Proteins
  • Placenta
  • Pregnancy
  • Premature Birth*
  • Stem Cells
  • TEA Domain Transcription Factors
  • Transcription Factors / genetics
  • Trophoblasts*

Substances

  • DNA-Binding Proteins
  • Muscle Proteins
  • TEA Domain Transcription Factors
  • TEAD4 protein, human
  • Transcription Factors