Reprogramming human endometrial fibroblast into induced pluripotent stem cells

Taiwan J Obstet Gynecol. 2012 Mar;51(1):35-42. doi: 10.1016/j.tjog.2012.01.008.

Abstract

Objective: A recent breakthrough demonstrated that ectopic expression of four genes is sufficient to reprogram human fibroblasts into inducible pluripotent stem cells (iPSCs). However, it remains unknown whether human endometrial fibroblasts (EMFs) are capable of being reprogrammed into EMF-derived iPSCs (EMF-iPSCs).

Methods: EMFs were obtained from donors in their third and fourth decade of life and were reprogrammed into iPSCs using retroviral transduction with Oct-4, Sox2, Klf4, and c-Myc.

Results: The EMF-iPSCs displayed the accelerated expression of endogenous Nanog and OCT-4 during reprogramming compared with EMFs. As a result, EMF-iPSC colonies that could be subcultured and propagated were established as early as 12 days after transduction. After 2 weeks of reprogramming, the human endometrial cells yielded significantly higher numbers of iPSC colonies and formed more 3D spheroid bodies than the EMFs. We have shown that human EMF-iPSCs are able to differentiate into neuronal-like cells, adipocytes, and osteocyte-like cells that express specific osteogenic genes.

Conclusion: Human EMFs can undergo reprogramming to establish pluripotent stem cell lines in female donors by the retroviral transduction of Oct-4, Sox2, Klf4, and c-Myc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adult
  • Cell Differentiation*
  • Cellular Reprogramming*
  • Endometrium*
  • Female
  • Homeodomain Proteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Karyotype
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Nanog Homeobox Protein
  • Neural Stem Cells / cytology
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Osteocytes / cytology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transduction, Genetic

Substances

  • Homeodomain Proteins
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MYC protein, human
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • SOX2 protein, human
  • SOXB1 Transcription Factors