转录性调节逻辑编排淋巴细胞和骨髓细胞命运决定
Rasoul Godini1,2, Jingjing Yan3, Michaël Chopin3
1Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, VIC, Australia.
Frontiers in immunology
|June 13, 2025
概括
这项研究解读了控制血细胞发育的基因调节网络,确定了决定淋巴细胞和髓状细胞命运的关键转录因子 (TF). 这些发现揭示了对免疫细胞分化至关重要的保护性调节元素.
科学领域:
- 血液形成和免疫学
- 基因调控和转录因子网络
- 细胞分化和血统承诺
背景情况:
- 造血干细胞 (HSC) 的分化是一个层次的过程,涉及连续的决策.
- 转录因子 (TF) 和它们的调节体密切控制血液和免疫细胞的发育.
- 了解血统特定的调节电路对于破译免疫细胞发育至关重要.
研究的目的:
- 解开控制B细胞,T细胞,先天性淋巴细胞 (ILCs) 和树突细胞 (DCs) 的特定基因调节电路.
- 确定血统受限的TFs,并构建免疫细胞发育的监管逻辑.
- 剖析保存的调节元素和TF表达模式,决定免疫细胞的特异性.
主要方法:
- 权重基因共同表达网络分析 (WGCNA) 用于识别与淋巴状或髓状细胞命运相关的基因模块.
- 对TF表达模式的分析,以确定受血统限制和广泛表达的因素.
- 基于TF表达式和保存元素的监管逻辑的构建.
主要成果:
- 识别控制B细胞,T细胞,ILC和DC发育的基因调控网络.
- 在ILCs,NK细胞和DCs之间发现了保存的调节元素.
- 详细剖析了常规和血细胞直流体中的调节元件.
结论:
- 这项研究为控制血细胞发育的调节机制提供了新的见解.
- 为了解血液形成中的分子机制,提供了一个监管蓝图.
- 这些发现突出了TF表达在决定免疫细胞系特异性的关键作用.
相关概念视频
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
General Transcription Factors
5.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.2K
Transcription
146.8K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
146.8K
Transcription Factors
75.7K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.7K
Combinatorial Gene Control
8.3K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.3K


