Department of Medicine.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Curr Opin Hematol. 2021 Jul 1;28(4):243-250. doi: 10.1097/MOH.0000000000000656.
Development and functions of hematopoietic stem cells (HSC) are regulated by multiple cellular components of the hematopoietic niche. Here we review the recent advances in studying the role of three such components -- osteoblasts, osteomacs, and megakaryocytes and how they interact with each other in the hematopoietic niche to regulate HSC.
Recent advances in transgenic mice models, scRNA-seq, transcriptome profile, proteomics, and live animal imaging have revealed the location of HSC within the bone and signaling molecules required for the maintenance of the niche. Interaction between megakaryocytes, osteoblasts and osteomacs enhances hematopoietic stem and progenitor cells (HSPC) function. Studies also revealed the niche as a dynamic entity that undergoes cellular and molecular changes in response to stress. Aging, which results in reduced HSC function, is associated with a decrease in endosteal niches and osteomacs as well as reduced HSC--megakaryocyte interactions.
Novel approaches to study the cellular components of the niche and their interactions to regulate HSC development and functions provided key insights about molecules involved in the maintenance of the hematopoietic system. Furthermore, these studies began to build a more comprehensive model of cellular interactions and dynamics in the hematopoietic niche.
造血干细胞(HSC)的发育和功能受到造血龛中多种细胞成分的调节。在这里,我们综述了研究三种这样的成分——成骨细胞、破骨细胞和成巨核细胞——以及它们如何在造血龛中相互作用以调节 HSC 的最新进展。
转基因小鼠模型、scRNA-seq、转录组谱、蛋白质组学和活体动物成像的最新进展揭示了 HSC 在骨内的位置以及维持龛所需的信号分子。巨核细胞、成骨细胞和成破骨细胞之间的相互作用增强了造血干细胞和祖细胞(HSPC)的功能。研究还揭示了龛是一个动态实体,它会响应应激而发生细胞和分子变化。导致 HSC 功能下降的衰老与骨内膜龛和破骨细胞减少以及 HSC-巨核细胞相互作用减少有关。
研究龛的细胞成分及其相互作用以调节 HSC 发育和功能的新方法提供了关于维持造血系统的分子的关键见解。此外,这些研究开始构建造血龛中细胞相互作用和动态的更全面模型。