Oct4-induced pluripotency in adult neural stem cells.
The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem cells (1F iPS) are similar to embryonic stem cells in vitro and in vivo. Not only can these cells can be efficiently differentiated into NSCs, cardiomyocytes, and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
Kim
Jeong Beom
JB
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, NRW, Germany.
Sebastiano
Vittorio
V
Wu
Guangming
G
Araúzo-Bravo
Marcos J
MJ
Sasse
Philipp
P
Gentile
Luca
L
Ko
Kinarm
K
Ruau
David
D
Ehrich
Mathias
M
van den Boom
Dirk
D
Meyer
Johann
J
Hübner
Karin
K
Bernemann
Christof
C
Ortmeier
Claudia
C
Zenke
Martin
M
Fleischmann
Bernd K
BK
Zaehres
Holm
H
Schöler
Hans R
HR
D053687:Adult Stem Cells / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology; D000090062:Kruppel-Like Factor 4; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D016256:Lewis X Antigen; D050814:Octamer Transcription Factor-3; D000469:Alkaline Phosphatase