Characterization of a new growth factor from a bone marrow vascular niche

项目总结/摘要 造血干细胞（HSC）和骨骼干细胞（SSC）在整个成人生活中持续存在，以维持 血液和骨骼系统中的稳态。HSC和SSC通常位于邻近 骨髓中的血管内皮细胞促进HSC和SSC的维持和功能， 可能是通过分泌生长因子。然而，骨髓中所有已知的HSC小生境因子更多地是 Leptin受体阳性（LepR+）血管周围基质细胞比内皮细胞表达丰富。 尚未发现HSC生长因子主要由骨髓内皮细胞产生。是 也不清楚内皮细胞是否分泌调节SSC维持的生长因子。鉴于 内皮细胞是骨髓血管的主要细胞成分，我们假设它们 可能分泌调节骨髓中HSC和/或SSC功能的因子。在这 在一项提议中，我将描述一种新的生长因子，它主要由骨中的内皮细胞合成 骨髓我的初步数据表明，Crispld 1缺失会消耗HSC/MPPs以及骨小梁 在骨髓里。这些数据表明，Crispld 1可以调节HSC和SSC的功能。 该因子的特性有可能为干细胞功能的调节提供新的见解 以及再生医学的新策略。

Project Summary/Abstract Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) persist throughout adult life to maintain homeostasis in the blood and skeletal systems, respectively. Both HSCs and SSCs usually localize adjacent to blood vessels in the bone marrow. Endothelial cells promote the maintenance and function of HSCs and SSCs, possibly by secreting growth factors. However, all known HSC niche factors in the bone marrow are more abundantly expressed by Leptin Receptor positive (LepR+) perivascular stromal cells than by endothelial cells. No HSC growth factors have yet been found to be produced primarily by bone marrow endothelial cells. It is also unclear whether endothelial cells secrete growth factors that regulate SSC maintenance. Given that endothelial cells are a prominent cellular component of bone marrow blood vessels, we hypothesize that they are likely to secrete factors that regulate the function of HSCs and/or SSCs in the bone marrow. In this proposal, I will characterize a new growth factor which is primarily synthesized by endothelial cells in the bone marrow. My preliminary data suggested that Crispld1 deletion depletes HSCs/MPPs as well as trabecular bone in the bone marrow. These data indicate that Crispld1 may regulate the function of both HSCs and SSCs. Characterization of this factor has the potential to provide new insights into the regulation of stem cell function as well as new strategies for regenerative medicine.