Open AccessIdentification of KLF9 and BCL3 as transcription factors that enhance reprogramming of primordial germ cells
Author(s) -
Kei Otsuka,
Asuka Takehara,
Natsuko Chiba,
Yasuhisa Matsui
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205004
Subject(s) - reprogramming , biology , transcription factor , microbiology and biotechnology , homeobox protein nanog , induced pluripotent stem cell , mef2c , embryonic stem cell , genetics , gene
Primordial germ cells (PGCs) are precursors of eggs and sperm. Although PGCs are unipotent cells in vivo , they are reprogrammed into pluripotent stem cells (PSCs), also known as embryonic germ cells (EGCs), in the presence of leukemia inhibitory factor and basic fibroblast growth factor (bFGF) in vitro . However, the molecular mechanisms responsible for their reprogramming are not fully understood. Here we show identification of transcription factors that mediate PGC reprogramming. We selected genes encoding transcription factors or epigenetic regulatory factors whose expression was significantly different between PGCs and PSCs with in silico analysis and RT-qPCR. Among the candidate genes, over-expression (OE) of Bcl3 or Klf9 significantly enhanced PGC reprogramming. Notably, EGC formation was stimulated by Klf9 -OE even without bFGF. G-protein-coupled receptor signaling-related pathways, which are involved in PGC reprogramming, were enriched among genes down-regulated by Klf9 -OE, and forskolin which activate adenylate cyclase, rescued repressed EGC formation by knock-down of Klf9 , suggesting a molecular linkage between KLF9 and such signaling.