Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2.
Inhibitor of DNA binding (Id) proteins function as inhibitors of members of the basic helix-loop-helix family of transcription factors and have been demonstrated to play an important role in regulating lymphopoiesis. However, the role of these proteins in regulation of myelopoiesis is currently unclear. In this study, we have investigated the role of Id1 and Id2 in the regulation of granulopoiesis. Id1 expression was initially up-regulated during early granulopoiesis, which was then followed by a decrease in expression during final maturation. In contrast, Id2 expression was up-regulated in terminally differentiated granulocytes. In order to determine whether Id expression plays a critical role in regulating granulopoiesis, Id1 and Id2 were ectopically expressed in CD34(+) cells by retroviral transduction. Our experiments demonstrate that constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced. Constitutive Id2 expression accelerates final maturation of both eosinophils and neutrophils, whereas inhibition of Id2 expression blocks differentiation of both lineages. Transplantation of beta2-microglobulin(-/-) nonobese diabetic severe combined immunodeficient (NOD/SCID) mice with CD34(+) cells ectopically expressing Id1 resulted in enhanced neutrophil development, whereas ectopic expression of Id2 induced both eosinophil and neutrophil development. These data demonstrate that both Id1 and Id2 play a critical, although differential role in granulopoiesis.
Buitenhuis
Miranda
M
Department of Pulmonary Diseases, University Medical Center, Utrecht, The Netherlands.
van Deutekom
Hanneke W M
HW
Verhagen
Liesbeth P
LP
Castor
Anders
A
Jacobsen
Sten Eirik W
SE
Lammers
Jan-Willem J
JW
Koenderman
Leo
L
Coffer
Paul J
PJ
D000818:Animals; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000502:physiology; D004804:Eosinophils / Q000166:cytology; D006098:Granulocytes / Q000166:cytology*; D018257:Helix-Loop-Helix Motifs; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D016688:Mice, Inbred NOD; D038042:Myelopoiesis; D009504:Neutrophils / Q000166:cytology; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014161:Transduction, Genetic
D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497450:ID2 protein, human; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors