IL-3 induces inhibitor of DNA-binding protein-1 in hemopoietic progenitor cells and promotes myeloid cell development.
Hemopoiesis depends on the expression and regulation of transcription factors, which control the maturation of specific cell lineages. We found that the helix-loop-helix transcription factor inhibitor of DNA-binding protein 1 (Id1) is not expressed in hemopoietic stem cells (HSC), but is increased in more committed myeloid progenitors. Id1 levels decrease during neutrophil differentiation, but remain high in differentiated macrophages. Id1 is expressed at low levels or is absent in developing lymphoid or erythroid cells. Id1 expression can be induced by IL-3 in HSC during myeloid differentiation, but not by growth factors that promote erythroid and B cell development. HSC were transduced with retroviral vectors that express Id1 and were transplanted in vivo to evaluate their developmental potential. Overexpression of Id1 in HSC promotes myeloid but impairs B and erythroid cell development. Enforced expression of Id1 in committed myeloid progenitor cells inhibits granulocyte but not macrophage differentiation. Therefore, Id1 may be part of the mechanism regulating myeloid vs lymphoid/erythroid cell fates, and macrophage vs neutrophil maturation.
Leeanansaksiri
Wilairat
W
Basic Research Program, Science Applications International Corporation (SAIC)-Frederick, National Cancer Institute-Frederick, MD 21702, USA.
Wang
Hui
H
Gooya
John M
JM
Renn
Katie
K
Abshari
Mehrnoosh
M
Tsai
Schickwann
S
Keller
Jonathan R
JR
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051798:Inhibitor of Differentiation Protein 1; D007377:Interleukin-3 / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D007377:Interleukin-3; D012097:Repressor Proteins; D014157:Transcription Factors