细胞谱系决定是发育生物学研究的核心科学问题之一。目前，骨骼肌细胞谱系决定的分子机制不十分清楚，长非编码RNA可能在这一过程中发挥重要调控作用。申请人鉴定了一个受MyoD调控、骨骼肌细胞特异表达、与MyoD结合调控肌细胞谱系决定的长非编码RNA Linc-RAM （Linc-RNA Activator of Myogenesis）。本项目利用实验室已制备的Linc-RAM-/-、MyoD-/-和Linc-RAM-/-;MyoD-/-小鼠及遗传示踪小鼠（如Rosa26-YFP），采用多种策略与方法探讨Linc-RAM对早期胚胎发育中肌细胞谱系的调控功能和机制，特别是Linc-RAM自身表达调控的机制。本项目的关键科学问题是揭示Linc-RAM调控肌细胞谱系决定的分子机制和Linc-RAM在决定MyoD调控靶基因特异性中的机制。研究结果将为阐明长非编码RNA在细胞谱系决定中的功能提供重要依据。

Cell lineage specification is one of the fundamental scientific questions in developmental biology. The molecular mechanism underlining myogenic cell specification is far from complete. Recent findings suggest tissue-specific expressed long non-coding RNA (LncRNA) may regulate cell lineage specification during development. Interestingly, our laboratory has previously identified a MyoD-regulated lncRNA (Linc-RNA Activator of Myogenesis, Linc-RAM), which is specifically expressed in skeletal muscle. Functionally, we demonstrate Linc-RAM directly binds MyoD and activates myogenic gene expression during myogenic lineage specification. The specific focus of the project is to investigate the function and molecular mechanism of Linc-RAM and its transcriptional regulation during embryonic myogenesis. Hopefully, we will decipher the molecular mechanism underlining functions of Linc-RAM in regulating myogenic lineage specification. In addition, we will provide significantly data to understand the molecular mechanism underlining functional specificity of the master transcriptional factor MyoD on target gene expression.