Gao Hongjuan, Wu Xiaorong, Fossett Nancy
Center for Vascular and Inflammatory Diseases and Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Genesis. 2011 Mar;49(3):105-16. doi: 10.1002/dvg.20711. Epub 2011 Mar 5.
Studies using Drosophila have contributed significantly to our understanding of regulatory mechanisms that control stem cell fate choice. The Drosophila blood cell progenitor or prohemocyte shares important characteristics with mammalian hematopoietic stem cells, including quiescence, niche dependence, and the capacity to form all three fly blood cell types. This report extends our understanding of prohemocyte fate choice by showing that the zinc-finger protein Odd-skipped promotes multipotency and blocks differentiation. Odd-skipped was expressed in prohemocytes and downregulated in terminally differentiated plasmatocytes. Furthermore, Odd-skipped maintained the prohemocyte population and blocked differentiation of plasmatocytes and lamellocytes but not crystal cells. A previous study showed that Odd-skipped expression is downregulated by Decapentaplegic signaling. This report provides a functional basis for this regulator/target pair by suggesting that Decapentaplegic signaling limits Odd-skipped expression to promote prohemocyte differentiation. Overall, these studies are the basis for a gene regulatory model of prohemocyte cell fate choice.
利用果蝇进行的研究极大地增进了我们对控制干细胞命运选择的调控机制的理解。果蝇血细胞祖细胞或前血细胞与哺乳动物造血干细胞具有重要的共同特征，包括静止、对微环境的依赖性以及形成所有三种果蝇血细胞类型的能力。本报告通过表明锌指蛋白Odd-skipped促进多能性并阻断分化，扩展了我们对前血细胞命运选择的理解。Odd-skipped在前血细胞中表达，在终末分化的浆细胞中下调。此外，Odd-skipped维持了前血细胞群体，并阻断了浆细胞和扁平细胞的分化，但不影响晶体细胞的分化。先前的一项研究表明，Odd-skipped的表达受Decapentaplegic信号通路下调。本报告通过表明Decapentaplegic信号通路限制Odd-skipped的表达以促进前血细胞分化，为这种调节因子/靶标对提供了功能基础。总体而言，这些研究是前血细胞命运选择基因调控模型的基础。
