Division of Hematology/Medical Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; and.
Division of Hematopathology, Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN.
Blood Adv. 2018 May 22;2(10):1130-1145. doi: 10.1182/bloodadvances.2017015073.
The CD34CD8α, sinusoid lining, littoral cells (LCs), and CD34CD8α, splenic vascular endothelial cells (SVECs) represent 2 distinct cellular types that line the vessels within normal spleens and those of patients with myelofibrosis (MF). To further understand the respective roles of LCs and SVECs, each was purified from normal and MF spleens, cultured, and characterized. Gene expression profiling indicated that LCs were a specialized type of SVEC. LCs possessed a distinct gene expression profile associated with cytoskeleton regulation, cellular interactions, endocytosis, and iron transport. LCs also were characterized by strong phagocytic activity, less robust tube-forming capacity and a limited proliferative potential. These characteristics underlie the role of LCs as cellular filters and scavengers. Although normal LCs and SVECs produced overlapping as well as distinct hematopoietic factors and adhesion molecules, the gene expression profile of MF LCs and SVECs distinguished them from their normal counterparts. MF SVECs were characterized by activated interferon signaling and cell cycle progression pathways and increased vascular endothelial growth factor receptor, angiopoietin-2, stem cell factor, interleukin (IL)-33, Notch ligands, and IL-15 transcripts. In contrast, the transcription profile of MF LCs was associated with mitochondrial dysfunction, reduced energy production, protein biosynthesis, and catabolism. Normal SVECs formed in vitro confluent cell layers that supported MF hematopoietic colony formation to a greater extent than normal colony formation. These data provide an explanation for the reduced density of LCs observed within MF spleens and indicate the role of SVECs in the development of extramedullary hematopoiesis in MF.
CD34CD8α、窦内皮细胞、边缘区细胞（LCs）和 CD34CD8α、脾血管内皮细胞（SVECs）代表了两种不同的细胞类型，分别位于正常脾脏和骨髓纤维化（MF）患者的血管内。为了进一步了解 LCs 和 SVECs 的各自作用，我们从正常和 MF 脾脏中纯化了这两种细胞进行培养和鉴定。基因表达谱分析表明，LCs 是一种特殊的 SVEC。LCs 具有独特的基因表达谱，与细胞骨架调节、细胞间相互作用、内吞作用和铁转运有关。LCs 还具有较强的吞噬活性、较弱的管状形成能力和有限的增殖潜力。这些特征是 LCs 作为细胞过滤器和清道夫的作用基础。虽然正常的 LCs 和 SVECs 产生重叠和独特的造血因子和黏附分子，但 MF LCs 和 SVECs 的基因表达谱将它们与正常细胞区分开来。MF SVECs 的特征是干扰素信号和细胞周期进展途径的激活，以及血管内皮生长因子受体、血管生成素-2、干细胞因子、白细胞介素（IL）-33、Notch 配体和 IL-15 转录本的增加。相比之下，MF LCs 的转录谱与线粒体功能障碍、能量产生减少、蛋白质生物合成和分解代谢有关。正常 SVECs 在体外形成了更有利于 MF 造血集落形成的致密细胞层，而正常集落形成则较少。这些数据为 MF 脾脏中观察到的 LCs 密度降低提供了解释，并表明 SVECs 在 MF 中骨髓外造血的发展中的作用。
