■造血干细胞中与自我更新调节因子相关的内在因素是众所周知的;然而,关于外在因素的信息有限,如细胞环境。因此,在这项研究中,我们分析了造血干细胞自我更新的调控机制,专注于成骨细胞生态位,并检查了对成骨细胞的粘附如何影响干细胞分化。
■对于本实验研究,我们开发了造血干细胞和成骨细胞的共培养系统,这样粘附于成骨细胞的细胞可以与不粘附于成骨细胞的细胞分离。将鼠Sca1阳性细胞根据它们是否附着于成骨细胞或从成骨细胞中脱离而进行分组。然后对每组进行集落测定和骨髓移植实验。
■粘附的Sca1阳性细胞比未粘附的Sca1阳性细胞产生更多的次级集落。此外,在骨髓移植实验中,粘附的Sca1阳性细胞显示成功植入。我们探索了Polycomb基因在细胞命运调节中的作用,发现附着于成骨细胞的自我更新细胞具有高Bmi-1表达和低Mel-18表达。而这种表达在分化细胞中逆转。
■我们的结果表明,造血干细胞在细胞分裂后保留在成骨细胞壁龛中时会自我更新。Further,当干细胞离开壁龛时,他们经历了分化。
UNASSIGNED: Intrinsic factors related to self-renewal regulatory factors in hematopoietic stem cells are well known; however, limited information is available on extrinsic factors, such as the cell environment. Therefore, in this study, we analyzed the regulatory mechanism of hematopoietic stem cell self-renewal, focusing on the osteoblastic niche, and examined how adherence to osteoblasts affects stem cell differentiation.
UNASSIGNED: For this experimental study, we developed a co-culture system for hematopoietic stem cells and osteoblasts, such that cells adhered to osteoblasts can be separated from those that do not. Murine Sca1-positive cells were separated into groups according to whether they were attached to osteoblasts or detached from osteoblasts, and each group was then subjected to colony assays and bone marrow transplantation experiments.
UNASSIGNED: Adhered Sca1-positive cells developed more secondary colonies than non-adhered Sca1-positive cells. Furthermore, in bone marrow transplantation experiments, adhered Sca1-positive cells showed successful engraftment. We explored the role of Polycomb genes in the regulation of cell fate and found that self-renewing cells attached to osteoblasts had high Bmi-1 expression and low Mel-18 expression, while this expression was reversed in differentiating cells.
UNASSIGNED: Our results suggest that hematopoietic stem cells self-renew when they remain in osteoblastic niches after cell division. Further, when stem cells leave the niches, they undergo differentiation.