Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Center for Preclinical Studies and Technology, Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland.
Stem Cell Rev Rep. 2019 Dec;15(6):785-794. doi: 10.1007/s12015-019-09920-4.
Hematopoietic stem cells (HSCs) are the best-characterized stem cells in adult tissues. Nevertheless, as of today, many open questions remain. First, what is the phenotype of the most primitive "pre-HSC" able to undergo asymmetric divisions during ex vivo expansion that gives rise to HSC for all hemato-lymphopoietic lineages. Next, most routine in vitro assays designed to study HSC specification into hematopoietic progenitor cells (HPCs) for major hematopoietic lineages are based on a limited number of peptide-based growth factors and cytokines, neglecting the involvement of several other regulators that are endowed with hematopoietic activity. Examples include many hormones, such as pituitary gonadotropins, gonadal sex hormones, IGF-1, and thyroid hormones, as well as bioactive phosphosphingolipids and extracellular nucleotides (EXNs). Moreover, in addition to regulation by stromal-derived factor 1 (SDF-1), trafficking of these cells during mobilization or homing after transplantation is also regulated by bioactive phosphosphingolipids, EXNs, and three ancient proteolytic cascades, the complement cascade (ComC), the coagulation cascade (CoA), and the fibrinolytic cascade (FibC). Finally, it has emerged that bone marrow responds by "sterile inflammation" to signals sent from damaged organs and tissues, systemic stress, strenuous exercise, gut microbiota, and the administration of certain drugs. This review will address the involvement of these unconventional regulators and present a broader picture of hematopoiesis.
造血干细胞（HSCs）是成人组织中研究最为透彻的干细胞。然而，时至今日，仍有许多悬而未决的问题。首先，在体外扩增过程中能够进行不对称分裂从而产生所有造血淋巴谱系造血干细胞的最原始“前 HSC”的表型是什么。其次，大多数旨在研究造血干细胞向造血祖细胞（HPCs）定向分化为主要造血谱系的常规体外检测方法基于有限数量的基于肽的生长因子和细胞因子，而忽略了其他一些具有造血活性的调节因子的参与。例如，许多激素，如垂体促性腺激素、性腺性激素、IGF-1 和甲状腺激素，以及生物活性磷酸鞘脂和细胞外核苷酸（EXN）。此外，除了基质衍生因子 1（SDF-1）的调节作用外，这些细胞在动员或移植后归巢过程中的迁移也受到生物活性磷酸鞘脂、EXN 和三种古老的蛋白水解级联（补体级联、凝血级联和纤维蛋白溶解级联）的调节。最后，人们发现骨髓对来自受损器官和组织、全身应激、剧烈运动、肠道微生物群和某些药物的信号会产生“无菌性炎症”反应。本综述将探讨这些非传统调节因子的参与，并呈现更广泛的造血图景。
