造血干细胞移植后的长期低血象状态严重影响受者生存质量，此状态直接取决于受者造血重建。骨髓血管龛是造血的场所，移植中骨髓窦内皮细胞受损直接影响血管龛功能，其恢复是造血重建的关键，Dll4/Notch信号通路调控有效的血管再生，然而其转录调控的探索匮乏。长链非编码RNA是基因表达调控的新着眼点，我们发现长链非编码RNA Gm14207与Notch配体Dll4高度同源；移植中骨髓窦内皮细胞内Gm14207与Dll4同步下降，二者呈正相关，提示Gm14207是Dll4的正性调节子。故本课题拟在明确0610009E02Rik调控Notch1表达的基础上，建立内皮细胞损伤离体和在体模型，进一步探索Gm14207在骨髓血管再生中的作用，从表观遗传及蛋白翻译等方面探索其调控Dll4的表达机制，拓宽人们对Notch信号通路的认识，深入解析骨髓血管龛重建的机理，为移植受者长期低血象的临床研究提供实验依据。

Prolonged low hemogram after hematopoietic stem cell transplantation (HSCT) which is dependent on recipients’ hematopoietic reconstitution seriously affects their quality of life. Damaged bone marrow sinusoidal endothelial cells during HSCT would directly influence the function of vascular niche, whose recovery is critical for hematopoietic reconstitution as bone marrow vascular niche regulates hematopoiesis. Dll4/Notch signaling is reported to regulate the regeneration of effective blood vessels and the mechanism by how this signaling works regarding transcriptional regulation remains unclear. Long non-coding RNA (lncRNA) has recently been identified as the new player in regulation of gene expression. Our previous study found that lncRNA Gm14207 has a higher homology to Dll4,a Notch ligand and their expression in bone marrow sinusoidal endothelial cells were decreased simultaneously and also positively correlated, suggesting Gm12407 is a positive regulator of Dll4. In this project, on the basis of understanding of the regulation of Notch1 expression by 0610009E02Rik, we propose to establish ex and in vivo model of endothelial cell damage to further investigate the role of Gm12407 in the regeneration of bone marrow blood vessels as well as the mechanism by how it regulates Dll4 expression from the aspect of epigenetic and protein translation, to broaden the knowledge on Notch1 signaling pathway. Deep analysis of the mechanism of bone marrow vascular niche reconstitution will provide experimental evidence for clinical studies on the prolonged low hemogram in recipients after HSCT.