Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells.
The ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety.
Ohm
Joyce E
JE
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Mali
Prashant
P
Van Neste
Leander
L
Berman
David M
DM
Liang
Liang
L
Pandiyan
Kurinji
K
Briggs
Kimberly J
KJ
Zhang
Wei
W
Argani
Pedram
P
Simons
Brian
B
Yu
Wayne
W
Matsui
William
W
Van Criekinge
Wim
W
Rassool
Feyruz V
FV
Zambidis
Elias
E
Schuebel
Kornel E
KE
Cope
Leslie
L
Yen
Jonathan
J
Mohammad
Helai P
HP
Cheng
Linzhao
L
Baylin
Stephen B
SB
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D005347:Fibroblasts / Q000502:physiology; D020869:Gene Expression Profiling; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000473:pathology / Q000502:physiology*
D002843:Chromatin