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Reprogramming in vivo produces teratomas and iPS cells with totipotency features
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Journal Article
Reprogramming in vivo produces teratomas and iPS cells with totipotency features
2013
Overview
Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of
in vivo
reprogramming within tissues. Here we show that transitory induction of the four factors
Oct4, Sox2, Klf4
and
c-Myc
in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur
in vivo
. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of
in situ
reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed
in vivo
. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these
in vivo
generated iPS cells are closer to embryonic stem cells (ES cells) than standard
in vitro
generated iPS cells. Moreover,
in vivo
iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of
in vivo
iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming
in vivo
is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine.
Induced pluripotent stem cells (iPS cells) have been created
in vivo
by reprogramming mouse somatic cells with
Oct4
,
Sox2
,
Klf4
and
c-Myc
; these cells have totipotent features that are missing from
in vitro
created iPS cells or embryonic stem cells.
In vivo
production of iPS cells
Manuel Serrano and colleagues show for the first time that reprogramming of somatic cells to pluripotency by the classic 'Yamanaka factors' Oct4, Sox2, Klf4 and c-Myc can be achieved
in vivo
. Analysis of induced pluripotent stem (iPS) cells induced
in vivo
from stomach, intestine, pancreas and kidney cells in mice shows that they are closer to embryonic stem cells than
in vitro
-generated iPS cells. The
in vivo
iPS cells also have the potential to generate embryo-like structures that express embryonic and extraembryonic markers, which suggests that they have totipotent features not found in conventional iPS or embryonic stem cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Cellular Reprogramming - genetics
/ Embryoid Bodies - metabolism
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - metabolism
/ Female
/ Humanities and Social Sciences
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Kruppel-Like Transcription Factors - genetics
/ Kruppel-Like Transcription Factors - metabolism
/ Male
/ Mice
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Rodents
/ Science
/ SOXB1 Transcription Factors - genetics
/ SOXB1 Transcription Factors - metabolism
/ Totipotent Stem Cells - cytology
/ Totipotent Stem Cells - metabolism
/ Tumors
