NLRP1对造血干细胞移植中损伤骨髓血管niche重构的调控作用

植入功能不良是造血干细胞移植（HSCT）严重并发症，影响移植受者的生存率与生存质量。良好的骨髓血管niche是HSC植入的必要条件，而移植后血管niche严重受损，损伤niche的重构状况决定HSC植入情况，但目前损伤血管niche的重构机理尚不清楚。我们前期研究发现，NLRP1在血管niche中高表达，参与血管niche的炎性损伤与功能调控。故推测：NLRP1是血管niche的潜在调控子，调控移植后血管niche的重构及造血重建。为此，本研究拟建立小鼠HSCT模型，获取高度纯化的骨髓微环境细胞，采用单细胞测序技术，从血管niche细胞群体表型、转录组特征及功能评估等方面，探索NLRP1对移植后损伤血管niche的调控作用及其对造血重建的影响。如获成功，则将从损伤血管niche重构层面进一步解析HSCT造血重建的调控机理，为深入探索HSCT植入功能不良的发生机理提供新思路。

Poor graft failure is a serious complication of hematopoietic stem cell transplantation (HSCT), which affects the survival rate and quality of life of transplant recipients. A good bone marrow vascular niche is a necessary condition for HSC engraftment. After transplantation, bone marrow vascular niche is severely damaged. The reconstruction status of the damaged vascular niche determines the status of HSC engraftment. However, the current reconstruction status and mechanism of the damaged vascular niche are not clear. Our previous research found that NLRP1 is highly expressed in bone marrow vascular niche, not only involved in bone marrow inflammatory injury, but also involved in the regulation of vascular niche function. It is speculated that NLRP1 is a potential regulator of bone marrow vascular niche and regulates vascular niche remodeling and hematopoietic reconstruction after transplantation. Based on this, our study intends to establish a mouse HSCT model and obtains highly purified bone marrow microenvironment cells to explore the regulatory effect of NLRP1 on injured bone marrow vascular niche and hematopoietic reconstruction after transplantation using single-cell sequencing technology from three aspects: vascular niche cell population phenotype, transcriptome characteristics, and functional evaluation. If succeed, it will further uncover the regulatory mechanism of bone marrow hematopoietic reconstitution after HSCT from the level of remodeling of damaged vascular niche and provide new ideas for further exploration of the mechanism of poor graft failure after HSCT.