期刊
ACTA HAEMATOLOGICA
卷 122, 期 4, 页码 230-237出版社
KARGER
DOI: 10.1159/000253591
关键词
Hematopoiesis; Hematopoietic progenitor cells; Megakaryocytes thrombocytopenia; Stem cell biology
类别
资金
- University of Wisconsin
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI064234] Funding Source: NIH RePORTER
Background/Aims: Despite a sophisticated understanding of the hematopoietic developmental program at the transcriptional level, our understanding of the role of E3 ubiquitin ligases remains underdeveloped. The E3 ubiquitin ligase, GRAIL (RNF128), is expressed in the bone marrow, but its role is as yet undefined. In this study, we evaluate the effect of GRAIL expression during hematopoietic differentiation in vitro and in vivo. Methods: Retroviral transduction of hematopoietic multipotent progenitor cells was used for methylcellulose colony assays and bone marrow reconstitution. Results: Enforced expression of GRAIL in colony assays demonstrated skewing of hematopoietic lineage development toward granulocytic/monocytic cells. Bone marrow reconstitution experiments with progenitor cells expressing biologically varied levels of GRAIL demonstrated diminished erythropoiesis and megakaryopoiesis if GRAIL ( endogenous or forced) is maintained throughout hematopoiesis. Conclusion: These data highlight a role for GRAIL during hematopoiesis and emphasize the importance of studying post-translational effects to complement our current understanding of the transcriptional regulation of hematopoiesis. Copyright (C) 2009 S. Karger AG, Basel
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