TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells

Ralph P Schneider, Ianire Garrobo, Miguel Foronda, Jose A Palacios, Rosa M Marión, Ignacio Flores, Sagrario Ortega, Maria A Blasco

Research output: Contribution to journalArticlepeer-review

Abstract

TRF1 is a component of the shelterin complex that protects chromosome ends. TRF1 deficiency leads to early embryonic lethality and to severe organ atrophy when deleted in adult tissues. Here we generate a reporter mouse carrying a knock-in eGFP-TRF1 fusion allele to study the role of TRF1 in stem cell biology and tissue homeostasis. We find that eGFP-TRF1 expression in mice is maximal in known adult stem cell compartments and show that TRF1 ensures their functionality. eGFP-TRF1 is highly expressed in induced pluripotent stem cells, uncoupled from the telomere elongation associated with reprogramming. Selection of eGFP-TRF1-high induced pluripotent stem cells correlates with higher pluripotency as indicated by their ability to form teratomas and chimeras. We further show that TRF1 is necessary for both induction and maintenance of pluripotency, and that TRF1 is a direct transcriptional target of Oct3/4.

Original languageEnglish
Pages (from-to)1946
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 2013

Keywords

  • Adult Stem Cells
  • Alleles
  • Animals
  • Atrophy
  • Biomarkers
  • Cell Compartmentation
  • Cell Nucleus
  • Cellular Reprogramming
  • Chromosomal Instability
  • Clone Cells
  • Fluorescence
  • Gene Deletion
  • Gene Knock-In Techniques
  • Green Fluorescent Proteins
  • Homeodomain Proteins
  • Induced Pluripotent Stem Cells
  • Intestine, Small
  • Mice
  • Octamer Transcription Factor-3
  • Promoter Regions, Genetic
  • Protein Binding
  • Recombinant Fusion Proteins
  • Skin
  • Telomere
  • Telomeric Repeat Binding Protein 1

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