Cebpa is required for haematopoietic stem and progenitor cell generation and maintenance in zebrafish.

IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Open Biology Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI:10.1098/rsob.240215
Kemin Chen, Jieyi Wu, Yuxian Zhang, Wei Liu, Xiaohui Chen, Wenqing Zhang, Zhibin Huang
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Abstract

The CCAAT enhancer binding protein alpha (CEBPA) is crucial for myeloid differentiation and the balance of haematopoietic stem and progenitor cell (HSPC) quiescence and self-renewal, and its dysfunction can drive leukemogenesis. However, its role in HSPC generation has not been fully elucidated. Here, we utilized various zebrafish cebpa mutants to investigate the function of Cebpa in the HSPC compartment. Co-localization analysis showed that cebpa expression is enriched in nascent HSPCs. Complete loss of Cebpa function resulted in a significant reduction in early HSPC generation and the overall HSPC pool during embryonic haematopoiesis. Interestingly, while myeloid differentiation was impaired in cebpa N-terminal mutants expressing the truncated zP30 protein, the number of HSPCs was not affected, indicating a redundant role of Cebpa P42 and P30 isoforms in HSPC development. Additionally, epistasis experiments confirmed that Cebpa functions downstream of Runx1 to regulate HSPC emergence. Our findings uncover a novel role of Cebpa isoforms in HSPC generation and maintenance, and provide new insights into HSPC development.

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斑马鱼造血干细胞和祖细胞的生成和维持需要 Cebpa。
CCAAT增强子结合蛋白α(CEBPA)对于髓系分化以及造血干细胞和祖细胞(HSPC)的静止和自我更新的平衡至关重要,其功能障碍可导致白血病的发生。然而,它在 HSPC 生成中的作用尚未完全阐明。在这里,我们利用各种斑马鱼 cebpa 突变体来研究 Cebpa 在 HSPC 区系中的功能。共定位分析表明,cebpa的表达富集在新生的HSPC中。Cebpa 功能的完全丧失导致胚胎造血过程中早期 HSPC 的生成和整个 HSPC 池的显著减少。有趣的是,在表达截短的 zP30 蛋白的 cebpa N 端突变体中,虽然髓系分化受损,但 HSPC 的数量却不受影响,这表明 Cebpa P42 和 P30 同工酶在 HSPC 发育中起着多余的作用。此外,外显子实验证实,Cebpa 在 Runx1 的下游发挥作用,调控 HSPC 的出现。我们的发现揭示了 Cebpa 同工酶在 HSPC 生成和维持中的新作用,并为 HSPC 的发育提供了新的见解。
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来源期刊
Open Biology
Open Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
10.00
自引率
1.70%
发文量
136
审稿时长
6-12 weeks
期刊介绍: Open Biology is an online journal that welcomes original, high impact research in cell and developmental biology, molecular and structural biology, biochemistry, neuroscience, immunology, microbiology and genetics.
期刊最新文献
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