Progress in the production of haematopoietic stem and progenitor cells from human pluripotent stem cells.
Progress in the production of haematopoietic stem and progenitor cells from human pluripotent stem cells.
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DOI：
10.1016/j.regen.2021.100050
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Forrester LM
中科院分区：
文献类型：
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作者：
Fidanza A;Forrester LM
细胞疗法目前用于治疗许多血液病。这些治疗包括使用最有效的造血干细胞（HSC）长期重建整个造血系统，以及使用成熟的功能性终末细胞（如携氧红细胞和免疫系统细胞）进行短期拯救，这些细胞可以对抗感染和修复组织。供应的限制和传播感染的风险促使设计方案以从人类多能干细胞（hPSC）产生这些细胞类型中的一些。虽然已经证明直接从hPSC产生最有效的HSC具有挑战性，但在开发可以成功产生造血祖细胞和大多数成熟细胞谱系的分化方案方面已经取得了重大进展。我们回顾了从hPSC生产造血干细胞和祖细胞（HSPC）的关键步骤，以及用于定义特定转换的细胞表面标记和报告策略。大多数研究都依赖于使用已知的标志物来定义体内HSPC的产生，但最近单细胞RNA测序已经允许采用偏差较小的方法来表征HSPC。转录谱分析已经确定了幼稚和定型hPSC衍生的HSPC群体的新标志物，并且轨迹分析提供了对其谱系潜力的新见解。体外和体内衍生的RNA单细胞测序数据集的直接比较突出了两个系统之间的相似性和差异性，这种更深入的理解将是设计和跟踪改进和更有效的分化方案的关键。
Cell therapies are currently used to treat many haematological diseases. These treatments range from the long-term reconstitution of the entire haematopoietic system using the most potent haematopoietic stem cells (HSCs) to the short-term rescue with mature functional end cells such as oxygen-carrying red blood cells and cells of the immune system that can fight infection and repair tissue. Limitations in supply and the risk of transmitting infection has prompted the design of protocols to produce some of these cell types from human pluripotent stem cells (hPSCs). Although it has proven challenging to generate the most potent HSCs directly from hPSCs, significant progress has been made in the development of differentiation protocols that can successfully produce haematopoietic progenitor cells and most of the mature cell lineages. We review the key steps used in the production of haematopoietic stem and progenitor cells (HSPCs) from hPSCs and the cell surface markers and reporter strategies that have been used to define specific transitions. Most studies have relied on the use of known markers that define HSPC production in vivo but more recently single cell RNA sequencing has allowed a less biased approach to their characterisation. Transcriptional profiling has identified new markers for naïve and committed hPSC-derived HSPC populations and trajectory analyses has provided novel insights into their lineage potential. Direct comparison of in vitro- and in vivo-derived RNA single cell sequencing datasets has highlights similarities and differences between the two systems and this deeper understanding will be key to the design and the tracking of improved and more efficient differentiation protocols.