一个单细胞的AML地图揭示了与年龄相关的基因调节网络在t(8;21) AML
Jessica Whittle1,2, Stefan Meyer3,4,5, Georges Lacaud2
1Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
eLife
|February 11, 2026
概括
这项研究创建了急性髓性白血病 (AML) 的最大单细胞转录组图集,揭示了AML中与年龄相关的基因特征. BCLAF1成为一个关键的预后指标,特别是在儿科病例中.
科学领域:
- 血液学 血液学 血液学
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 急性髓性白血病 (AML) 呈现出显著的细胞和遗传异质,影响临床结果.
- 现有的单细胞RNA测序 (scRNA-seq) 研究由于对比分析的样本大小小,存在局限性.
- 需要一个全面的单细胞转录基因资源来探索AML多样性.
研究的目的:
- 通过整合各种数据集,构建人类AML最大的单细胞转录基因地图.
- 调查与年龄相关的基因调控网络 (GRN) 签名在t(8;21) AML.
- 为了确定AML的潜在预后生物标志物.
主要方法:
- 在20项研究中,大规模整合了来自159名AML患者和51名健康捐赠者的748,679个细胞.
- 使用集成的scRNA-seq数据分析t(8;21) AML中特定年龄的GRN特征.
- 使用大量RNA测序和多原子数据集 (scRNA-seq和scATAC-seq) 验证增强器驱动的GRNs.
主要成果:
- 含有748,679个细胞的AML scAtlas代表了人类AML最大的单细胞资源.
- 在t(8;21) AML中确定了年龄相关的GRN特征,这表明与胎儿/未成熟的造血干细胞起源相关的差异.
- 发现BCLAF1在儿科t(8;21) 推断出子宫内起源的AML中被丰富,并显示出预后潜力.
结论:
- 该AML scAtlas是研究AML分子机制和异质性的宝贵资源.
- 年龄相关的基因调节在t(8;21) AML中起作用,可能与发育起源有关.
- BCLAF1是特定的AML亚型的有前途的预后生物标志物.
相关概念视频
02:02Cis-regulatory Sequences
11.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.9K
02:02Cis-regulatory Sequences
4.2K
4.2K
01:58Cell Specific Gene Expression
16.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.6K
02:26Protein Networks
4.6K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.6K
02:18Network Covalent Solids
16.2K
Network covalent solids contain a three-dimensional network of covalently bonded atoms as found in the crystal structures of nonmetals like diamond, graphite, silicon, and some covalent compounds, such as silicon dioxide (sand) and silicon carbide (carborundum, the abrasive on sandpaper). Many minerals have networks of covalent bonds.
To break or to melt a covalent network solid, covalent bonds must be broken. Because covalent bonds are relatively strong, covalent network solids are typically...
To break or to melt a covalent network solid, covalent bonds must be broken. Because covalent bonds are relatively strong, covalent network solids are typically...
16.2K
01:42What is Gene Expression?
197.0K
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
197.0K