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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1208-1215.
Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2006-01-010199.
 Previous Article | Next Article 
Submitted January 13, 2006
Accepted March 26, 2006
Unique effects of STAT3 on the early phase of
hematopoietic stem cell regeneration
Yang-Jo Chung, Bo-Bae Park, Young-Ju Kang, Tae-Min Kim, Connie J Eaves, and Il-Hoan Oh*
The Catholic University of Korea, Medical School, The Catholic Cell Therapy Center
TThe Catholic University of Korea, Medical School, The Catholic Cell Therapy Center
Terry Fox Lab, British Columbia Cancer Agency, Canada
* Corresponding author; email: iho{at}catholic.ac.kr.
Self-renewal of hematopoietic stem cells (HSCs) is key
to their reconstituting ability, but the signaling
pathways that regulate this process remain poorly
understood. Here we show that transduction of adult
mouse bone marrow cells with a constitutively activated
form of STAT3 (STAT3-C) increased their regenerative
activity in lethally irradiated recipients. Conversely,
transduction of these cells with a dominant negative
form of STAT3 suppressed their regenerative activity.
Serial transplantation and clonal tracking of the HSC
progeny regenerated in vivo from STAT3-C-transduced HSCs
demonstrated that the major effect of forced expression
of STAT3-C was to enhance HSC self-renewal during the
initial phase of hematopoietic recovery. This acquired
potential for enhanced self-renewal divisions then
became latent, but was reactivated when the cells were
transferred to new irradiated recipients. Increased
levels of activated STAT3 were also found to be
associated with greater preservation of primitive
hematopoietic cells in short term cultures. These
results indicate a novel biphasic regulation of HSC self-
renewal in vivo in which activated STAT3 promotes HSC
self-renewal under stimulated, but not homeostatic
conditions. STAT3 may thus be an important regulator of
hematopoietic regeneration and a novel target for HSC
engineering.
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