2001 Fiscal Year Final Research Report Summary
Transcriptional regulation of eosinophil development
| Project/Area Number |
12670412
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
IWAMA Atsushi Inst. Basic Medical Sciences, University of Tsukuba, Assistant Professor, 基礎医学系, 講師 (70244126)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Eosinophil / C / EBP / GATA-1 / RFX |
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| Research Abstract |
The molecular mechanisms governing eosinophil development remain largely unknown. In this study, we analyzed roles of transcription factors, C/EBP, GATA and RFX in this process. We retrovirally transduced these transcription factor genes into human CD34-positive hematopoietic progenitors and analyzed the effects of transduced genes on the cell differentiation. A dominant negative C/EBP completely blocked the granulocyte/macrophage commitment of human myeloid progenitors. Alternatively, Langerhans cell (LC) commitment was markedly facilitated in the absence of TNFα, a strong inducer of Langerhans cell development. Conversely, expression of wild-type C/EBP myeloid progenitors promoted eosinophilic differentiation and completely inhibited TNFα-dependent LC development. On the other hand, enforced expression of GATA-1 in human primary myeloid progenitor cells completely switched myeloid cell fate into eosinophils. Expression of GATA-1 exclusively promoted development and terminal maturation of eosinophils. Importantly, GATA-1-deficient mice failed to develop eosinophil progenitors in the fetal liver. Additionally, GATA-2 also showed instructive capacity comparable to GATA-1 vitro and efficiently compensated for GATA-1-deficiency in terms of eosinophil development in vivo, indicating that proper accumulation of GATA factors is critical for eosinophil development. All these data clearly show that the expression of GATA-1 in combination with C/EBPα could be the critical determinant for eosinophil lineage commitment.
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Research Products
(10 results)
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[Publications] Iwama A, Osawa M, Hirasawa R, Uchiyama N, Keneko S, Onodera M, Shibuya K, Shibuya A, Vinson C, Tenen DG, Nakauchi H: "Reciprocal roles for C/EBP and PU.1 transcription factors in Langerhans cell commitment"J. Exp. Med.. (in press). (2002)
Description
「研究成果報告書概要(欧文)」より
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