Benayahu Dafna, Shefer Gabi, Shur Irena
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Ann Anat. 2009 Jan;191(1):2-12. doi: 10.1016/j.aanat.2008.07.008. Epub 2008 Sep 10.
Utilizing adult stem cells for regenerative medicine of skeletal tissues requires the development of molecular and biochemical tools that will allow isolation of these cells and direction of their differentiation towards a desired lineage and tissue formation. Stem cell commitment and fate decision into specialized functional cells involve coordinated activation and silencing of lineage-specific genes. Transcription factors and chromatin-remodeling proteins are key players in the control process of lineage commitment and differentiation during embryogenesis and adulthood. Transcription factors act in cooperation with co-regulator proteins to generate tissue-specific responses that elicits the tissue specific gene expression. Consequently, one of the main challenges of today's research is to characterize molecular pathways that coordinate the lineage-specific differentiation. Epigenetic regulation includes chromatin remodeling that control structural changes of DNA required for the binding of transcription factors to promoter regions. Revealing the mechanisms of action of such factors will provide understanding of how transcription and chromatin regulatory factors function together to regulate stem cell lineage fate decision.
利用成体干细胞进行骨骼组织的再生医学需要开发分子和生化工具,以便能够分离这些细胞,并引导它们向所需的谱系分化以及形成组织。干细胞向特定功能细胞的定向和命运决定涉及谱系特异性基因的协同激活和沉默。转录因子和染色质重塑蛋白是胚胎发育和成年期谱系定向和分化控制过程中的关键参与者。转录因子与共调节蛋白协同作用,产生引发组织特异性基因表达的组织特异性反应。因此,当今研究的主要挑战之一是表征协调谱系特异性分化的分子途径。表观遗传调控包括染色质重塑,其控制转录因子与启动子区域结合所需的DNA结构变化。揭示这些因子的作用机制将有助于理解转录和染色质调节因子如何共同发挥作用来调节干细胞谱系命运决定。