Dyskeratosis congenita (DKC) is caused by mutations in genes that control telomere homeostasis, and is characterised by clinical symptoms ranging from bone marrow failure to pulmonary fibrosis and cancer. Disease features vary with the affected gene, but are all thought to result from defects in the function of tissue stem cells. Although mouse models have provided some insight regarding underlying mechanisms, human studies are an essential component of research on DKC and will be required for developing new therapies. Batista et al. report that induced pluripotent stem cells (iPSCs) derived from fibroblasts of patients with DKC exhibit defects that mirror the biochemical features of the patients’ cells, including impaired telomere homeostasis. The authors probed distinct pathological mechanisms underlying the disease using iPSCs derived from five patients carrying diverse mutations (in TERT, TCAB1 and DKC1), and found that the extent of the defects observed in the iPSCs correlated with clinical disease severity. The findings suggest that restoring telomere homeostasis in tissue stem cells might be a promising therapy for DKC. They also support the application of iPSC-based systems to study other diseases caused by stem-cell defects.

Batista
L. F. Z
,
Pech
M. F.
,
Zhong
F. L.
,
Nguyen
H. N.
,
Xie
K. T.
,
Zaug
A. J.
,
Crary
S. M.
,
Choi
J.
,
Sebastiano
V.
,
Cherry
A.
, et al. 
(
2011
).
Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells
.
Nature
[Epub ahead of print] .

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