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Forced expression of Nanog in hematopoietic stem cells results in a γδT-cell disorder

Authors :
Tanaka, Yosuke
Era, Takumi
Nishikawa, Shin-ichi
Kawamata, Shin
Source :
Blood; July 2007, Vol. 110 Issue: 1 p107-115, 9p
Publication Year :
2007

Abstract

Nanog is a key molecule involved in the maintenance of the self-renewal of undifferentiated embryonic stem (ES) cells. In this work we investigate whether Nanog can 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) hematopoietic stem cells (HSCs) invariantly develop a unique disorder typified by an atrophic thymus occupied by Nanog-expressing γδT-cell receptor–positive (TCR+) cells (Nanog T cells). All thymi are eventually occupied by Nanog T cells with CD25+CD44+surface phenotype that home selectively to the thymus on 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 γδT-cell malignancy.

Details

Language :
English
ISSN :
00064971 and 15280020
Volume :
110
Issue :
1
Database :
Supplemental Index
Journal :
Blood
Publication Type :
Periodical
Accession number :
ejs57129917
Full Text :
https://doi.org/10.1182/blood-2006-08-039628