title: TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells.
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.
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Schneider
authors.forename: Ianire
authors.initials: I
authors.lastname: Garrobo
authors.forename: Miguel
authors.initials: M
authors.lastname: Foronda
authors.forename: Jose A
authors.initials: JA
authors.lastname: Palacios
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Marión
authors.forename: Ignacio
authors.initials: I
authors.lastname: Flores
authors.forename: Sagrario
authors.initials: S
authors.lastname: Ortega
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001284:Atrophy; D015415:Biomarkers / Q000378:metabolism; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D065150:Cellular Reprogramming; D043171:Chromosomal Instability; D002999:Clone Cells; D005453:Fluorescence; D017353:Gene Deletion; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007421:Intestine, Small / Q000473:pathology; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology; D016615:Telomere / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; D011993:Recombinant Fusion Proteins; D035321:Telomeric Repeat Binding Protein 1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins