Submitted August 21, 2006
Accepted March 11, 2007
Forced expression of Nanog in hematopoietic stem cells results in a 
T cell disorder
Yosuke Tanaka, Takumi Era, Shin-ichi Nishikawa, and Shin Kawamata*
Riken Center for Developmental Biology, Kobe, Japan
Foundation for Biomedical Research & Innovation, Kobe, Japan
* Corresponding author; email: kawamata{at}fbri.org.
Nanog is a key molecule involved in the maintenance of the self-renewal of undifferentiated ES cells. In this work we investigate whether Nanog has the ability to enhance self-renewal in hematopoietic stem cells. Contrary to our expectation, no positive effect of Nanog transduction was detected in bone marrow reconstitution assays. However, recipients of nanog-transduced (Nanog°) HSC invariantly develop a unique disorder typified by an atrophic thymus occupied by Nanog-expressing 
TCR+ cells (Nanog°T cells). All thymi are eventually occupied by Nanog°T cells with CD25+CD44+ surface phenotype, home selectively to the thymus upon transfer, and suppress normal thymocyte development, which is partly ascribed to destruction of the microenvironment in the thymus cortex. Moreover, this initial disorder invariantly develops to a lymphoproliferative disorder, in which Nanog°T cells undergo unlimited proliferation in the peripheral lymphoid tissues and eventually kill the host. This invariable end-result suggests that Nanog is a candidate oncogene for T cell malignancy.
