TY - JOUR
T1 - Integrative Analysis of the Acquisition of Pluripotency in PGCs Reveals the Mutually Exclusive Roles of Blimp-1 and AKT Signaling
AU - Nagamatsu, Go
AU - Saito, Shigeru
AU - Takubo, Keiyo
AU - Suda, Toshio
N1 - Funding Information:
We thank Dr. A. Tarakhovsky (Rockefeller University) for providing the Blimp-1 flox/flox mice and Dr. T. Nakano and Dr. T. Kimura (Osaka University) for providing the AKT-Mer mice. We also thank Dr. K. Hosokawa (Kyushu University) for providing the recombinant CRE protein and Dr. K. Hayashi (Kyushu University) for a critical reading of this manuscript. This study was supported in part by a grant from the Project for Realization of Regenerative Medicine . Support for the Core Institutes for iPS Cell Research was provided by MEXT and the Keio University Medical Science Fund . G.N. was supported by a PRESTO grant of the Japan Science and Technology Agency and by Funds for the Development of Human Resources in Science and Technology of the Program to Disseminate a Tenure Tracking System for the Tenure-Track Program at the Sakaguchi Laboratory.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/7/14
Y1 - 2015/7/14
N2 - Primordial germ cells (PGCs) are lineage-restricted unipotent cells that can dedifferentiate into pluripotent embryonic germ cells (EGCs). Here we performed whole-transcriptome analysis during the conversion of PGCs into EGCs, a process by which cells acquire pluripotency. To examine the molecular mechanism underlying this conversion, we focused on Blimp-1 and Akt, which are involved in PGC specification and dedifferentiation, respectively. Blimp-1 overexpression in embryonic stem cells suppressed the expression of downstream targets of the pluripotency network. Conversely, Blimp-1 deletion in PGCs accelerated their dedifferentiation into pluripotent EGCs, illustrating that Blimp-1 is a pluripotency gatekeeper protein in PGCs. AKT signaling showed a synergistic effect with basic fibroblast growth factor plus 2i+A83 treatment on EGC formation. AKT played a major role in suppressing genes regulated by MBD3. From these results, we defined the distinct functions of Blimp-1 and Akt and provided mechanistic insights into the acquisition of pluripotency in PGCs.
AB - Primordial germ cells (PGCs) are lineage-restricted unipotent cells that can dedifferentiate into pluripotent embryonic germ cells (EGCs). Here we performed whole-transcriptome analysis during the conversion of PGCs into EGCs, a process by which cells acquire pluripotency. To examine the molecular mechanism underlying this conversion, we focused on Blimp-1 and Akt, which are involved in PGC specification and dedifferentiation, respectively. Blimp-1 overexpression in embryonic stem cells suppressed the expression of downstream targets of the pluripotency network. Conversely, Blimp-1 deletion in PGCs accelerated their dedifferentiation into pluripotent EGCs, illustrating that Blimp-1 is a pluripotency gatekeeper protein in PGCs. AKT signaling showed a synergistic effect with basic fibroblast growth factor plus 2i+A83 treatment on EGC formation. AKT played a major role in suppressing genes regulated by MBD3. From these results, we defined the distinct functions of Blimp-1 and Akt and provided mechanistic insights into the acquisition of pluripotency in PGCs.
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U2 - 10.1016/j.stemcr.2015.05.007
DO - 10.1016/j.stemcr.2015.05.007
M3 - Article
C2 - 26050930
AN - SCOPUS:84937526255
SN - 2213-6711
VL - 5
SP - 111
EP - 124
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -