The loss of cell differentiation is a phenomenon that takes place in
a physiological context. It occurs during tissue regeneration and also
in tumourigenesis. In fact, this is increasingly considered one of the
critical initial steps in cancer development.
During the 'in vivo' reprogramming process, cellular telomeres are
extended due to an increase in endogenous telomerase. This is the main
conclusion of a paper published in 'Stem Cell Reports
' by a
team from the Spanish National Cancer Research Center (CNIO).
‘Cell dedifferentiation induced by reprogramming involves telomere elongation by telomerase; the changes observed in this process also occur during the early stages of tumor development.’
observations show, for the first time, that the reprogramming of living
tissue results in telomerase activation and telomere elongation; thus
reversing one of the hallmarks of aging: 'the presence of short
"We have found that when you induce cell dedifferentiation in an
adult organism, the telomeres become longer, which is consistent with
cellular rejuvenation", explains María A. Blasco, head of the CNIO
Telomeres and Telomerase Group and leader of this research. This
lengthening of the telomeres is an unequivocal sign of cell
rejuvenation, which has been quantified for the first time here in a
Blasco and her colleagues have worked with the so-called
"reprogrammable mice" -created by Manuel Serrano, also a CNIO
researcher, whose group is also involved in this project. Broadly
speaking, the cells of these transgenic animals carry the four Yamanaka
factors (OSKM) whose expression is turned on when an antibiotic is
administered. In doing so, the cells regress to an embryonic-like state,
a condition known as known as pluripotency.
CHANGES MEDIATED BY TELOMERASE
In light of the importance of telomeres in tissue regeneration,
ageing and cancer, the authors decided to analyse the changes that occur
in these protective structures of the chromosomes during the 'in vivo'
reprogramming process, which leads to dedifferentiation of the tissues.
Their observations indicate that this process entails a lengthening of
the telomeres, a marker of cellular rejuvenation. This elongation
occurs, according to this research, due to the action of telomerase.
"What we have seen for the first time is the induction of telomerase
'in vivo'," explained Blasco and Rosa M. Marion, the leading authors of
the paper. "To date, we do not know of any study that describes the
induction of endogenous telomerase by defined transcription factors in
the context of adult tissues," say the authors.
SIMILARITIES WITH EARLY STAGES OF CANCER
Dedifferentiation induced by 'in vivo' reprogramming, as well as the
dedifferentiation associated with the initiation of cancer, involve
"similar changes in the telomeres", say the authors. In both of these
processes, we see the activation of telomerase and the subsequent
elongation of the telomeres.
A better knowledge of the changes described in the telomeres during
'in vivo' reprogramming and in pathological processes, such as cancer,
will improve our understanding about the molecular events associated
with cellular differentiation and, most likely, with other processes
that involve cell plasticity.