遗传 ›› 2025, Vol. 47 ›› Issue (5): 573-588.doi: 10.16288/j.yczz.24-288

• 研究报告 • 上一篇    下一篇

Lyl1不同转录本在斑马鱼原始造血中的作用

林杰豪(), 杨童舒, 张文清(), 刘伟()   

  1. 华南理工大学医学院，教育部发育与疾病医药基础研究创新中心，广州 510006
  • 收稿日期:2024-10-08 修回日期:2024-12-11 出版日期:2025-05-20 发布日期:2025-02-18
  • 通讯作者: 张文清，博士，教授，研究方向：人类疾病斑马鱼动物模型的建立、造血发育以及调控。E-mail: mczhangwq@scut.edu.cn；
    刘伟，博士，副教授，研究方向：人类疾病斑马鱼动物模型的建立、造血发育以及调控。E-mail: liuwei7@scut.edu.cn
  • 作者简介:林杰豪，硕士，专业方向：生物学。E-mail: 2213763056@qq.com
  • 基金资助:
    国家重点研发项目(2023YFA1800100)

Role of different Lyl1 transcripts in zebrafish primitive hematopoiesis

Jiehao Lin(), Tongshu Yang, Wenqing Zhang(), Wei Liu()   

  1. Development and Disease Medicine Basic Research Innovation Center, Ministry of Education, School of Medicine, South China University of Technology, Guangzhou 510006, China
  • Received:2024-10-08 Revised:2024-12-11 Published:2025-05-20 Online:2025-02-18
  • Supported by:
    National Key R&D Program of China(2023YFA1800100)

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摘要：

原始造血是生物体内至关重要的发育过程，其产生的血液细胞不仅在早期胚胎时期负责氧气和营养物质的运输，同时也为免疫系统发育奠定了基础。在原始造血过程中，造血相关转录因子及其辅因子相互作用形成复杂的调控网络，共同调控原始造血的发生与成熟。其中，bHLH转录因子家族中的SCL和LYL1在胚胎造血中起着核心作用。SCL参与原始造血的启动，而LYL1则被认为是SCL的旁系同源，能够在成年后SCL缺失时弥补其对造血的影响。然而，目前LYL1在原始造血中的具体作用尚不明确。本研究通过分析斑马鱼血液细胞单细胞RNA测序(scRNA-seq)数据，发现CABZ01066694.1在造血干/祖细胞中高表达。序列比对显示，CABZ01066694.1是lyl1基因的一种短型转录本。本研究通过 5′端快速扩增的cDNA末端测序(5′RACE)验证了斑马鱼和人类的lyl1基因均存在长型转录本(lyl1f)和短型转录本(lyl1s)。进一步通过分析公共数据库中的scRNA-seq和RNA-seq数据，发现在斑马鱼原始造血细胞中，lyl1主要转录lyl1s。最后，本研究通过Morpholino技术分别敲低lyl1f和lyl1s，发现lyl1s的敲低显著抑制了原始髓系祖细胞和原始粒系细胞的产生，而lyl1f的敲低则促进了原始巨噬细胞的生成。综上所述，本研究揭示了斑马鱼源lyl1和人源LYL1均存在长、短型转录本，并且这两种转录本在调控原始髓系的发生过程中具有不同作用，为理解原始造血的分子调控提供了新的线索。

关键词: Lyl1, 斑马鱼, 原始造血, 转录因子

Abstract:

Primitive hematopoiesis is a crucial process in the organism, responsible for the transportation of oxygen and nutrients during early embryonic stages and laying the foundation for the immune system. During primitive hematopoiesis, hematopoietic-related transcription factors and their cofactors interact to form a complex regulatory network that controls the process of primitive hematopoiesis. Among the bHLH transcription factor family, SCL and LYL1 are key factors in embryonic hematopoiesis. SCL is responsible for initiating primitive hematopoiesis, while LYL1, a paralog of SCL, compensates for the hematopoietic impact of SCL deficiency in adulthood. However, the role of LYL1 in primitive hematopoiesis remains unclear. This study, through analysis of zebrafish blood cell scRNA-seq data, discovered high expression of CABZ01066694.1 in hematopoietic stem/progenitor cells. Sequence alignment revealed it as a short transcript of the lyl1 gene. Subsequently, using 5'RACE and sequencing, the study confirmed the existence of both long (lyl1f) and short (lyl1s) transcripts of lyl1 in zebrafish and humans, similar to mice. Further analysis of scRNA-seq and RNA-seq data from public databases showed that in zebrafish primitive hematopoietic cells, lyl1 primarily transcribes lyl1s. Finally, using Morpholino technology to knock down lyl1f and lyl1s separately, it was found that knocking down lyl1s hindered the production of primitive myeloid progenitors and primitive granulocytes, whereas knocking down lyl1f promoted the production of primitive macrophages. In conclusion, this study demonstrates the existence of long and short transcripts of lyl1 in zebrafish and humans, with distinct roles in regulating primitive myelopoiesis, providing new insights into the regulation of primitive hematopoiesis.

Key words: Lyl1, zebrafish, primitive hematopoiesis, transcription factor

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