Induced 2C Expression and Implantation-Competent Blastocyst-like Cysts from Primed Pluripotent Stem Cells

Stem Cell Reports. 2019 Sep 10;13(3):485-498. doi: 10.1016/j.stemcr.2019.07.011. Epub 2019 Aug 8.

Abstract

Soon after fertilization, the few totipotent cells of mammalian embryos diverge to form a structure called the blastocyst (BC). Although numerous cell types, including germ cells and extended-pluripotency stem cells, have been developed from pluripotent stem cells (PSCs) in vitro, generating functional BCs only from PSCs remains elusive. Here, we describe induced self-organizing 3D BC-like cysts (iBLCs) generated from mouse PSC culture. Resembling natural BCs, iBLCs have a blastocoel-like cavity and were formed with outer cells expressing trophectoderm lineage markers and with inner cells expressing pluripotency markers. iBLCs transplanted to pseudopregnant mice uteruses implanted, induced decidualization, and exhibited growth and development before resorption, demonstrating that iBLCs are implantation competent. iBLC precursor intermediates required the transcription factor Prdm14 and concomitantly activated the totipotency-related cleavage-stage MERVL reporter and 2C genes. Thus, our system may contribute to the understanding of molecular mechanisms underpinning totipotency, embryogenesis, and implantation.

Keywords: blastocyst; cell biology; cell plasticity; early embryo; implantation; pluripotent stem cells; reproduction; reprogramming; totipotency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Blastocyst / cytology
  • Blastocyst / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Lineage
  • DNA-Binding Proteins / metabolism
  • Embryonic Development
  • Female
  • Genes, Reporter
  • Mice
  • Mice, Inbred ICR
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / metabolism
  • Uterus / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Prdm14 protein, mouse
  • RNA-Binding Proteins
  • Transcription Factors
  • Yap1 protein, mouse