Open AccessThrombopoietin, flt3‐ligand and c‐kit‐ligand modulate HOX gene expression in expanding cord blood CD133 + cells
Author(s) -
McGuckin C. P.,
Forraz N.,
Pettengell R.,
Thompson A.
Publication year - 2004
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2004.00313.x
Subject(s) - haematopoiesis , hox gene , thrombopoietin , biology , progenitor cell , microbiology and biotechnology , stem cell , cord blood , myeloid , transcription factor , immunology , gene , genetics
. Haemopoietic stem/progenitor cell (HSPC) development is regulated by extrinsic and intrinsic stimuli. Extrinsic modulators include growth factors and cell adhesion molecules, whereas intrinsic regulation is achieved with many transcription factor families, of which the HOX gene products are known to be important in haemopoiesis. Umbilical cord blood CD133 + HSPC proliferation potential was tested in liquid culture with ‘TPOFLK’ (thrombopoietin, flt‐3 ligand and c‐kit ligand, promoting HSPC survival and self‐renewal), in comparison to ‘K36EG’ (c‐kit‐ligand, interleukins‐3 and ‐6, erythropoietin and granulocyte colony‐stimulating factor, inducing haemopoietic differentiation). TPOFLK induced a higher CD133 + HSPC proliferation (up to 60‐fold more, at week 8) and maintained a higher frequency of the primitive colony‐forming cells than K36EG. Quantitative polymerase chain reaction analysis revealed opposite expression patterns for specific HOX genes in expanding cord blood CD133 + HSPC. After 8 weeks in liquid culture, TPOFLK increased the expression of HOX B3 , B4 and A9 (associated with uncommitted HSPC) and reduced the expression of HOX B8 and A10 (expressed in committed myeloid cells) when compared to K36EG. These results suggest that TPOFLK induces CD133 + HSPC proliferation, self‐renewal and maintenance, up‐regulation of HOX B3 , B4 and A9 and down‐regulation of HOX B8 and A10 gene expression.