Regulation of the hematopoietic stem cell lifecycle by the endothelial niche.
Regulation of the hematopoietic stem cell lifecycle by the endothelial niche.
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DOI：
10.1097/moh.0000000000000350
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发表时间：
2017-07
影响因子：
3.2
通讯作者：
Butler JM
中科院分区：
文献类型：
--
作者：
Ramalingam P;Poulos MG;Butler JM
造血干细胞（HSC）在其整个生命周期中主要驻留在直接接触或紧密接近血管内皮的位置。从造血内皮细胞分化为HSC胚胎的那一刻起，内皮细胞（EC）就充当了一个关键的细胞枢纽，调节着对HSC在其整个生命周期中的维持至关重要的大量生物学过程。在这篇综述中，我们将讨论最近的研究结果在内皮生态位介导的调节HSC功能的发展，老化和再生条件。采用遗传血管模型的研究已经明确证实，内皮细胞在胚胎发育过程中以及在稳态和再生过程中成体HSC维持过程中为HSC的出现提供了必要的指导性线索。内皮细胞的老化可能会损害其维持HSC功能的能力，从而导致与衰老相关的造血缺陷的发展。这些发现为探索内皮细胞的治疗应用开辟了新的途径。EC可适于充当扩增真正HSC的指导性平台，并且还用作细胞疗法以促进骨髓抑制性和清髓性损伤后造血系统的再生。EC为在其整个生命周期中维持功能性HSC提供了肥沃的生态位。对EC-HSC串扰的更好理解将为开发用于改善衰老期间HSC功能的EC导向策略铺平道路。
Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions. Studies employing genetic vascular models have unequivocally confirmed that ECs provide the essential instructive cues for HSC emergence during embryonic development as well as adult HSC maintenance during homeostasis and regeneration. Aging of ECs may impair their ability to maintain HSC function contributing to the development of aging-associated hematopoietic deficiencies. These findings have opened up new avenues to explore the therapeutic application of ECs. ECs can be adapted to serve as an instructive platform to expand bona fide HSCs and also utilized as a cellular therapy to promote regeneration of the hematopoietic system following myelosuppressive and myeloablative injuries. ECs provide a fertile niche for maintenance of functional HSCs throughout their lifecycle. An improved understanding of the EC-HSC cross-talk will pave the way for development of EC-directed strategies for improving HSC function during aging.