Myeloid Cell Origins, Differentiation, and Clinical Implications.
Myeloid Cell Origins, Differentiation, and Clinical Implications.
复制标题
DOI：
10.1128/microbiolspec.mchd-0031-2016
复制
发表时间：
2016-10
影响因子：
3.7
通讯作者：
Weissman IL
中科院分区：
文献类型：
--
作者：
Weiskopf K;Schnorr PJ;Pang WW;Chao MP;Chhabra A;Seita J;Feng M;Weissman IL
造血干细胞(HSC)是一种驻留在骨髓中的多能干细胞，具有形成血液和免疫系统的所有细胞的能力。自从1988年首次纯化以来，更多的研究已经提炼了造血干细胞的表型和功能，并表征了它们的所有下游后代。造血谱分为两个主要分支：髓系臂和淋巴系臂。髓系臂以普通髓系祖细胞及其产生的所有细胞类型为特征。在小鼠和人类身上，已经确定了造血的阶段。在胚胎发育期间，最早的造血发生在卵黄囊血岛，然后迁移到胎儿肝脏和造血器官。一些成人髓系群体直接由卵黄囊前体细胞发展而来，没有明显的骨髓中间体，如组织驻留巨噬细胞。随着时间的推移，造血功能也会发生变化，随着动物年龄的增长，占主导地位的HSC偏向于髓系发育。骨髓生成缺陷会导致许多血液疾病，其中一些可以通过针对发育异常阶段的治疗来克服。此外，对髓系发育的洞察告诉了我们程序性细胞去除的机制。CD47Sirpα轴是一种髓系特异性免疫检查点，限制巨噬细胞清除造血干细胞，但可被血液病和实体恶性肿瘤利用。针对CD47的治疗代表了一种治疗癌症的新策略。总体而言，对造血和髓系细胞发育的了解对再生医学、造血细胞移植、恶性肿瘤和许多其他疾病都有意义。
The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the Common Myeloid Progenitor and all of its resulting cell types. The stages of hematopoiesis have been defined in both mice and humans. During embryological development, the earliest hematopoiesis takes place in yolk sac blood islands then migrates to the fetal liver and hematopoietic organs. Some adult myeloid populations develop directly from yolk sac progenitors without apparent bone marrow intermediates, such as tissue resident macrophages. Hematopoiesis also changes over time, with a bias of the dominating HSCs towards myeloid development as animals age. Defects in myelopoiesis contribute to many hematologic disorders, and some of these can be overcome with therapies that target the aberrant stage of development. Furthermore, insights into myeloid development have informed us of mechanisms of programmed cell removal. The CD47/SIRPα axis, a myeloid-specific immune checkpoint, limits macrophage removal of HSCs but can be exploited by hematologic and solid malignancies. Therapeutics targeting CD47 represent a new strategy for treating cancer. Overall, an understanding of hematopoiesis and myeloid cell development has implications for regenerative medicine, hematopoietic cell transplantation, malignancy, and many other diseases.