RRC ID 67666
Author Kinoshita T, Nagamatsu G, Saito S, Takubo K, Horimoto K, Suda T.
Title Telomerase reverse transcriptase has an extratelomeric function in somatic cell reprogramming.
Journal J Biol Chem
Abstract Reactivation of the endogenous telomerase reverse transcriptase (TERT) catalytic subunit and telomere elongation occur during the reprogramming of somatic cells to induced pluripotent stem (iPS) cells. However, the role of TERT in the reprogramming process is unclear. To clarify its function, the reprogramming process was examined in TERT-KO somatic cells. To exclude the effect of telomere elongation, tail-tip fibroblasts (TTFs) from first generation TERT-KO mice were used. Although iPS cells were successfully generated from TERT-KO TTFs, the efficiency of reprogramming these cells was markedly lower than that of WT TTFs. The gene expression profiles of iPS cells induced from TERT-KO TTFs were similar to those of WT iPS cells and ES cells, and TERT-KO iPS cells formed teratomas that differentiated into all three germ layers. These data indicate that TERT plays an extratelomeric role in the reprogramming process, but its function is dispensable. However, TERT-KO iPS cells showed transient defects in growth and teratoma formation during continuous growth. In addition, TERT-KO iPS cells developed chromosome fusions that accumulated with increasing passage numbers, consistent with the fact that TERT is essential for the maintenance of genome structure and stability in iPS cells. In a rescue experiment, an enzymatically inactive mutant of TERT (D702A) had a positive effect on somatic cell reprogramming of TERT-KO TTFs, which confirmed the extratelomeric role of TERT in this process.
Volume 289(22)
Pages 15776-87
Published 2014-5-30
DOI 10.1074/jbc.M113.536037
PII S0021-9258(20)38636-1
PMID 24733392
PMC PMC4140932
MeSH Animals Cell Differentiation / physiology Cells, Cultured Cellular Reprogramming / physiology* Chromosomal Instability / physiology Epigenesis, Genetic / genetics Fibroblasts / cytology Fibroblasts / enzymology* Gene Expression Regulation, Neoplastic Genomics Mice Mice, Knockout Mice, Nude Neoplasm Transplantation Tail / cytology Telomerase / genetics* Telomerase / metabolism* Telomere / physiology* Teratoma / enzymology* Teratoma / pathology
IF 4.238
DNA material CSII-EF-mTERT-IRES2-Venus (RDB12959)