CrxOS maintains the self-renewal capacity of murine embryonic stem cells.
Embryonic stem (ES) cells maintain pluripotency by self-renewal. Several homeoproteins, including Oct3/4 and Nanog, are known to be key factors in maintaining the self-renewal capacity of ES cells. However, other genes required for the mechanisms underlying this process are still unclear. Here we report the identification by in silico analysis of a homeobox-containing gene, CrxOS, that is specifically expressed in murine ES cells and is essential for their self-renewal. ES cells mainly express the short isoform of endogenous CrxOS. Using a polyoma-based episomal expression system, we demonstrate that overexpression of the CrxOS short isoform is sufficient for maintaining the undifferentiated morphology of ES cells and stimulating their proliferation. Finally, using RNA interference, we show that CrxOS is essential for the self-renewal of ES cells, and provisionally identify foxD3 as a downstream target gene of CrxOS. To our knowledge, ours is the first delineation of the physiological role of CrxOS in ES cells.
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Ryota
R
Saito
Tokiwa
T
Yamasaki
Yoko
Y
Nagai
Jinzhan
J
Wu
Hiroaki
H
Kajiho
Tadashi
T
Yokoi
Eiichiro
E
Noda
Sachiko
S
Nishina
Hitoshi
H
Niwa
Noriyuki
N
Azuma
Toshiaki
T
Katada
Hiroshi
H
Nishina
D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice
C546200:CrxOS protein, mouse; D018398:Homeodomain Proteins