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World J Stem Cells. Aug 26, 2016; 8(8): 251-259
Published online Aug 26, 2016. doi: 10.4252/wjsc.v8.i8.251
Reprogramming of germ cells into pluripotency
Yoichi Sekita, Toshinobu Nakamura, Tohru Kimura
Yoichi Sekita, Tohru Kimura, Laboratory of Stem Cell Biology, Department of Biosciences, Kitasato University School of Science, Kanagawa 252-0373, Japan
Toshinobu Nakamura, Laboratory of Epigenetic Regulation, Department of Animal Bioscience, Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan
Author contributions: Sekita Y, Nakamura T and Kimura T wrote all the sections.
Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and Takeda Science Foundation.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tohru Kimura, PhD, Professor, Laboratory of Stem Cell Biology, Department of Biosciences, Kitasato University School of Science, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan. tkimura@kitasato-u.ac.jp
Telephone: +81-042-7788864 Fax: +81-042-7788864
Received: April 26, 2016
Peer-review started: April 27, 2016
First decision: May 17, 2016
Revised: June 8, 2016
Accepted: July 11, 2016
Article in press: July 13, 2016
Published online: August 26, 2016
Processing time: 115 Days and 8.7 Hours
Abstract

Primordial germ cells (PGCs) are precursors of all gametes, and represent the founder cells of the germline. Although developmental potency is restricted to germ-lineage cells, PGCs can be reprogrammed into a pluripotent state. Specifically, PGCs give rise to germ cell tumors, such as testicular teratomas, in vivo, and to pluripotent stem cells known as embryonic germ cells in vitro. In this review, we highlight the current knowledge on signaling pathways, transcriptional controls, and post-transcriptional controls that govern germ cell differentiation and de-differentiation. These regulatory processes are common in the reprogramming of germ cells and somatic cells, and play a role in the pathogenesis of human germ cell tumors.

Keywords: Primordial germ cell; Embryonic germ cell; Germ cell tumor; Reprogramming; Induced pluripotent stem cell; Small molecule compound; Gene; Signal; Transcription factor

Core tip: Primordial germ cells can be reprogrammed into pluripotent stem cells called as embryonic germ cells in vitro and into pluripotent germ cell tumors in vivo. Germ cell reprogramming can be regulated by signaling pathways, including PI3K/Akt signaling, mitogen-activated protein kinase signaling, transforming growth factor-β signaling, RA signaling. These mechanisms are also involved in somatic cell reprogramming, indicating that there exist common regulatory networks regulating germ and somatic cell reprogramming. On the other hand, regulators for germ cell development prevent germ cell dedifferentiation in unique manners.