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正常和紊乱的人类红细胞生成中红系祖细胞的特征、调控及靶向作用

Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis.

作者信息

Dulmovits Brian M, Hom Jimmy, Narla Anupama, Mohandas Narla, Blanc Lionel

机构信息

aCenter for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset bDepartment of Molecular Medicine and Pediatrics, Hofstra Northwell School of Medicine, Hempstead, New York cDepartment of Pediatric Hematology/Oncology, Stanford University School of Medicine, Stanford, California dRed Cell Physiology Laboratory, New York Blood Center, New York, New York, USA.

出版信息

Curr Opin Hematol. 2017 May;24(3):159-166. doi: 10.1097/MOH.0000000000000328.

DOI:10.1097/MOH.0000000000000328
PMID:28099275
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5518670/
Abstract

PURPOSE OF REVIEW

The erythroid progenitors burst-forming unit-erythroid and colony-forming unit-erythroid have a critical role in erythropoiesis. These cells represent a heterogeneous and poorly characterized population with modifiable self-renewal, proliferation and differentiation capabilities. This review focuses on the current state of erythroid progenitor biology with regard to immunophenotypic identification and regulatory programs. In addition, we will discuss the therapeutic implications of using these erythroid progenitors as pharmacologic targets.

RECENT FINDINGS

Erythroid progenitors are classically characterized by the appearance of morphologically defined colonies in semisolid cultures. However, these prior systems preclude a more thorough understanding of the composite nature of progenitor populations. Recent studies employing novel flow cytometric and cell-based assays have helped to redefine hematopoiesis, and suggest that erythroid progenitors may arise from different levels of the hematopoietic tree. Moreover, the identification of cell surface marker patterns in human burst-forming unit-erythroid and colony-forming unit-erythroid enhance our ability to perform downstream functional and molecular analyses at the population and single cell level. Advances in these techniques have already revealed novel subpopulations with increased self-renewing capacity, roles for erythroid progenitors in globin gene expression, and insights into pharmacologic mechanisms of glucocorticoids and pomalidomide.

SUMMARY

Immunophenotypic and molecular characterization resolves the diversity of erythroid progenitors, and may ultimately lead to the ability to target these progenitors to ameliorate diseases of dyserythropoiesis.

摘要

综述目的

红系祖细胞红系爆式集落形成单位和红系集落形成单位在红细胞生成中起关键作用。这些细胞代表了一个异质性且特征描述不足的群体,具有可调节的自我更新、增殖和分化能力。本综述重点关注红系祖细胞生物学在免疫表型鉴定和调控程序方面的现状。此外,我们将讨论将这些红系祖细胞用作药物靶点的治疗意义。

最新发现

传统上,红系祖细胞的特征是在半固体培养中出现形态学上定义的集落。然而,这些先前的系统妨碍了对祖细胞群体复合性质的更深入理解。最近采用新型流式细胞术和基于细胞的检测方法的研究有助于重新定义造血作用,并表明红系祖细胞可能起源于造血树的不同层次。此外,在人类红系爆式集落形成单位和红系集落形成单位中细胞表面标志物模式的鉴定增强了我们在群体和单细胞水平进行下游功能和分子分析的能力。这些技术的进步已经揭示了具有增强自我更新能力的新型亚群、红系祖细胞在珠蛋白基因表达中的作用以及对糖皮质激素和泊马度胺药理机制的深入了解。

总结

免疫表型和分子特征解析了红系祖细胞的多样性,并最终可能导致有能力靶向这些祖细胞以改善红细胞生成异常疾病。

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本文引用的文献

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Pure red cell aplasia.纯红细胞再生障碍。
Blood. 2016 Nov 24;128(21):2504-2509. doi: 10.1182/blood-2016-05-717140.
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TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors.转化生长因子-β抑制剂通过增强红系爆式集落形成单位(BFU-E)红系祖细胞的自我更新来刺激红细胞生成。
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造血干细胞的发现:揭示集落形成单位测定法的历史与未来前景
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