通过五系输出偏差分析揭示非人灵长类的造血干细胞异质性。

IF 1.5 Q3 HEMATOLOGY 血液科学(英文) Pub Date : 2024-01-10 eCollection Date: 2024-01-01 DOI:10.1097/BS9.0000000000000176
Man Zhang, Di Liu, Yu Lan, Bing Liu, Zongcheng Li, Yanli Ni
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引用次数: 0

摘要

了解造血干细胞的异质性对治疗恶性血液疾病至关重要。与小鼠相比,我们对人类造血干细胞异质性的了解十分有限。幸运的是,非人灵长类动物(NHP)已成为研究人类造血干细胞的最佳动物模型。在这里,我们使用了一个来自非人灵长类动物自体骨髓移植的公开数据集,重点研究了在两个时间点(11/12 个月和/或 42/43 个月)总共 820 个具有重组能力的造血干细胞克隆的所有可用的五个系(粒细胞、单核细胞、B 细胞、T 细胞和自然杀伤细胞)。有趣的是,对这些克隆进行无监督聚类发现了六种造血干细胞亚型,包括一种淋巴细胞/骨髓细胞平衡亚型(LM-平衡)和五种单系偏向亚型。我们还观察到,这些造血干细胞克隆的亚型可能会随着时间的推移而发生变化,特定亚型可能会转变为其他五种亚型中的任何一种,尽管具有一定程度的选择性。特别是,六种亚型中的每一种都更有可能转变为淋巴细胞型而非髓细胞型。此外,我们的五系分类方法与传统的淋巴/骨髓偏向分类方法有很强的相关性。具体来说,我们的粒细胞偏向和单核细胞偏向亚型主要归因于α-造血干细胞,而LM平衡、B细胞偏向和T细胞偏向亚型主要与β-造血干细胞有关。γ-造血干细胞由B细胞偏向亚型和T细胞偏向亚型的一小部分组成。总之,我们的五系分类根据系输出偏向确定了更精细的造血干细胞亚型。这些发现丰富了我们对 NHPs 中造血干细胞异质性的认识,并为人类研究提供了重要启示。
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Hematopoietic stem cell heterogeneity in non-human primates revealed by five-lineage output bias analysis.

Understanding hematopoietic stem cell (HSC) heterogeneity is crucial for treating malignant blood disorders. Compared with mice, we have limited knowledge of the heterogeneity of human HSCs. Fortunately, non-human primates (NHPs) have become the best animal models for studying human HSCs. Here, we employed a public dataset derived from NHP autologous bone marrow transplantation, and focused on a total of 820 HSC clones with reconstitution capacity of all available five lineages (granulocyte, monocyte, B cell, T cell, and natural killer cell) at two time points (11/12 and/or 42/43 months). Intriguingly, unsupervised clustering on these clones revealed six HSC subtypes, including a lymphoid/myeloid balanced (LM-balanced) subtype and five single-lineage-biased subtypes. We also observed that the subtypes of these HSC clones might change over time, and a given subtype could transition into any one of the other five subtypes, albeit with a certain degree of selectivity. Particularly, each of the six subtypes was more likely to turn into lymphoid-biased rather than myeloid-biased ones. Additionally, our five-lineage classification method exhibited strong correlation with traditional lymphoid/myeloid bias classification method. Specifically, our granulocyte- and monocyte-biased subtypes were predominantly attributed to α-HSCs, while LM-balanced, B cell-biased, and T cell-biased subtypes were primarily associated with β-HSCs. The γ-HSCs were composed of a small subset of B cell-biased and T cell-biased subtypes. In summary, our five-lineage classification identifies more finely tuned HSC subtypes based on lineage output bias. These findings enrich our understanding of HSC heterogeneity in NHPs and provide important insights for human research.

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