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.

Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease

“…13 Similar findings can be observed in patients with dyskeratosis congenita, a disease characterized by altered telomere maintenance. Dyskeratosis congenita patients show signs of enteropathy and apoptosis because of premature critical shortening of telomeres.…”

Genome-wide analysis ofin vivoTRF1 binding to chromatin restricts its location exclusively to telomeric repeats

“…15 Even so, we previously published a TRF1 ChIP-seq done in induced Pluripotent Stem (iPS) cells, which display high TRF1 levels, showing no significant TRF1 binding to putative regulatory regions nor intragenic binding of this protein outside telomeric regions. 29 Given our negative findings with TRF1, it would be interesting to study the genome-wide DNA binding profiles for TRF2, other shelterin that binds to double-stranded DNA and recruits RAP1 to telomeres. In fact, we previously demonstrated that TRF2 binds to TTAGGG-rich extra-telomeric RAP1 binding sites.…”

The 68-kDa Telomeric Repeat Binding Factor 1 (TRF1)-associated Protein (TAP68) Interacts with and Recruits TRF1 to the Spindle Pole during Mitosis

“…Further studies will evaluate the effects of TAP68 silencing on cell proliferation as greater cell proliferation was observed with TRF1 lox/lox mice (16). TAP68 suppression may also influence cell cycle progression.…”

“…For example, TRF1 expression correlates with stem cell pluripotency (16). The functional involvement of TRF1 in mitosis is well established.…”