Hedgehog signaling and cell cycle control in differentiating erythroid progenitors.
Hedgehog (Hh) signaling regulates differentiation in numerous systems, but its functions in the control of hematopoietic differentiation have not been extensively explored. Initial studies have indicated that hedgehog signaling affects the proliferation and differentiation of erythroid progenitors (Detmer, K., et al., Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling. Blood Cells Mol. Dis. 26(4) (2000) 360-372). To examine the effect of Hh signaling on the erythroid developmental program at the molecular level, Hh signaling in committed erythroid progenitors differentiating in vitro was inhibited, and the appearance/disappearance of molecular markers of erythroid differentiation was monitored. The expression timetable for CD34, CD36, the erythropoietin receptor, and glycophorin A was retarded in the absence of Hh signaling. Hemoglobinization was delayed and decreased relative to controls. Morphological changes of erythroid maturation were also delayed. The fraction of cells in S-phase was decreased during the initial period of exponential expansion as assessed by propidium iodide staining and flow cytometry, as was the rate of tritiated thymidine incorporation. A modest decrease in the proliferation rate was observed. These results suggest that Hh signaling is one of the mechanisms in the regulation of erythroid proliferation and differentiation.
Detmer
Kristina
K
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA. detmer_km@mercer.edu
Thompson
Angela J
AJ
Garner
Ronald E
RE
Walker
Anna N
AN
Gaffield
William
W
Dannawi
Hassan
H
D015415:Biomarkers; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism*; D006021:Glycophorins / Q000378:metabolism; D053823:Hedgehog Proteins; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology
D015415:Biomarkers; D006021:Glycophorins; D053823:Hedgehog Proteins; D006454:Hemoglobins; D015534:Trans-Activators; D014704:Veratrum Alkaloids; C000541:cyclopamine