Upregulation of the Drosophila Friend of GATA gene U-shaped by JAK/STAT signaling maintains lymph gland prohemocyte potency.
Studies using Drosophila melanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in third-instar lymph gland prohemocytes and downregulated in a subpopulation of differentiating blood cells. Genetic analyses indicated that U-shaped maintains the prohemocyte population by blocking differentiation. In addition, activated STAT directly regulated ush expression as evidenced by results from loss- and gain-of-function studies and from analyses of the u-shaped hematopoietic cis-regulatory module. Collectively, these findings identify U-shaped as a downstream effector of the posterior signaling center, establishing a novel link between the stem cell niche and the intrinsic regulation of potency and differentiation. Given the functional conservation of Friend of GATA proteins and the role that GATA factors play during cell fate choice, these factors may regulate essential functions of vertebrate hematopoietic stem cells, including processing signals from the stem cell niche.
Gao
Hongjuan
H
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Room 215, 800 W. Baltimore Street, Baltimore, MD 21201, USA.
Wu
Xiaorong
X
Fossett
Nancy
N
D000818:Animals; D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D004789:Enzyme Activation; D053263:Gene Regulatory Networks; D017344:Genes, Insect; D006410:Hematopoiesis; D006434:Hemocytes / Q000166:cytology* / Q000201:enzymology; D053612:Janus Kinases / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000201:enzymology; D009154:Mutation / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
D015415:Biomarkers; D029721:Drosophila Proteins; C508614:FOG protein, Drosophila; D050791:STAT Transcription Factors; D014157:Transcription Factors; C109258:ush protein, Drosophila; D053612:Janus Kinases