TY - JOUR
T1 - Constitutively active β-catenin confers multilineage differentiation potential on lymphoid and myeloid progenitors
AU - Baba, Yoshihiro
AU - Garrett, Karla P.
AU - Kincade, Paul W.
N1 - Funding Information:
We thank Viji Dandapani, Jacob Bass, and Diana Hamilton for expert technical assistance. In addition, we appreciate the secretarial help provided by Shelli Wasson. This work was supported by grants AI20069 and AI58162 from the National Institutes of Health and P20-RR15577 from the COBRE Program of the National Center for Research Resources. P.W.K. holds the William H. and Rita Bell Endowed Chair in Biomedical Research.
PY - 2005/12
Y1 - 2005/12
N2 - β-catenin-mediated Wnt signaling may contribute to the self-renewal of hematopoietic stem cells and proliferation in some malignancies. We now show that expression of constitutively active β-catenin in normal lymphoid or myeloid progenitors generated uncommitted cells with multilineage differentiation potential. Inappropriate gene expression occurred in cells destined to produce either cell type and caused corresponding changes in their characteristics. For example, forced activation of β-catenin quickly increased C/EBPα while reducing EBF and Pax-5 in lymphoid progenitors that then generated myeloid cells. Inversely, EBF dramatically increased in transduced myeloid progenitors and lymphocytes were produced. The results indicate that ectopic activation of β-catenin destabilizes lineage fate decisions and confers some, but not all, stem cell properties on committed progenitors.
AB - β-catenin-mediated Wnt signaling may contribute to the self-renewal of hematopoietic stem cells and proliferation in some malignancies. We now show that expression of constitutively active β-catenin in normal lymphoid or myeloid progenitors generated uncommitted cells with multilineage differentiation potential. Inappropriate gene expression occurred in cells destined to produce either cell type and caused corresponding changes in their characteristics. For example, forced activation of β-catenin quickly increased C/EBPα while reducing EBF and Pax-5 in lymphoid progenitors that then generated myeloid cells. Inversely, EBF dramatically increased in transduced myeloid progenitors and lymphocytes were produced. The results indicate that ectopic activation of β-catenin destabilizes lineage fate decisions and confers some, but not all, stem cell properties on committed progenitors.
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U2 - 10.1016/j.immuni.2005.10.009
DO - 10.1016/j.immuni.2005.10.009
M3 - Article
C2 - 16356858
AN - SCOPUS:28844455024
SN - 1074-7613
VL - 23
SP - 599
EP - 609
JO - Immunity
JF - Immunity
IS - 6
ER -
