Constitutive activation of STAT5A promotes human hematopoietic stem cell self-renewal and erythroid differentiation.
Activation of the transcription factor signal transducer and activator of transcription (STAT)5 is involved in various aspects of hematopoiesis, affecting cell proliferation, differentiation, and cell survival. Constitutive activation of STAT5 has also been associated with leukemic transformation. We overexpressed the constitutively active mutant STAT5A(1*6) in human cord blood CD34+ cells and evaluated the effects on the hematopoietic potential of stem cells in a variety of in vitro and in vivo systems. The observed phenotypic changes were correlated with differential gene expression patterns induced by STAT5A(1*6). Our data indicate that a persistent activation of STAT5A in human hematopoietic stem and progenitor cells results in their enhanced self-renewal and diverts differentiation to the erythroid lineage.
Schuringa
Jan Jacob
JJ
Laboratory of Developmental Hematopoiesis, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Chung
Ki Young
KY
Morrone
Giovanni
G
Moore
Malcolm A S
MA
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007938:Leukemia / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008894:Milk Proteins / Q000378:metabolism*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins