Cellular components of the hematopoietic niche and their regulation of hematopoietic stem cell function.
Cellular components of the hematopoietic niche and their regulation of hematopoietic stem cell function.
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DOI：
10.1097/moh.0000000000000656
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发表时间：
2021-07-01
影响因子：
3.2
通讯作者：
Srour EF
中科院分区：
文献类型：
--
作者：
Ghosh J;Koussa RE;Mohamad SF;Liu J;Kacena MA;Srour EF
造血干细胞（HSC）的发育和功能受造血生态位的多种细胞成分的调节。本文就成骨细胞、成骨细胞和巨核细胞在造血微环境中的相互作用及其对造血干细胞的调控作用作一综述。转基因小鼠模型、scRNA-seq、转录组图谱、蛋白质组学和活体动物成像的最新进展揭示了HSC在骨内的位置和维持生态位所需的信号分子。巨核细胞、成骨细胞和成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。研究还表明，生态位是一个动态实体，在应对压力时会发生细胞和分子变化。导致HSC功能降低的衰老与骨内膜龛和骨瘤的减少以及HSC-巨核细胞相互作用的减少有关。研究小生境的细胞组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参与造血系统维持的分子的关键见解。此外，这些研究开始建立一个更全面的造血生态位中的细胞相互作用和动力学模型。
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.