The gene encoding the hematopoietic stem cell regulator CCN3 (NOV) is under direct cytokine control through the transcription factors STAT5a/b.

ABSTRACT: Cytokines control the biology of hematopoietic stem and progenitor cells in part through the transcription factors STAT5a/b. CCN3/NOV has been reported as a positive regulator of hematopoietic stem and progenitor cells. We report microarray analyses of Lineage- Sca-1+ c-Kit+ (KSL) cells in the presence and absence of STAT5a/b. Expression of the ccn3 gene was induced over 100-fold in control, but not STAT5a/b-null cells, upon stimulation with a cocktail containing IL-3, IL-6, SCF, TPO and Flt3 ligand. Among the cytokines, IL-3 elevated ccn3 mRNA level in Lineage- c-Kit+ (KL) cells and 32D cells. ChIP assays using 32D cells revealed IL-3-induced binding of STAT5a/b to a GAS site in the ccn3 gene promoter. This is the first report to link two molecules with importance in the regulation of HSCs, CCN3 and STAT5a/b. We report that the regulation and expression of the ccn3 gene is directly controlled by IL-3 through the transcription factors STAT5a/b. Six Control and Six Stat5a/b-null KSL cells, including three biological replications, were unstimulated or stimulated with a cocktail containing IL-3, IL-6, SCF, TPO and FL.

ORGANISM(S): Mus musculus

SUBMITTER: WeiPing Chen 

PROVIDER: E-GEOD-20684 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress