在出生后的大脑发育过程中,基因组结构和转录动态的变化与感官体验无关
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在PubMed上查看摘要
概括
此摘要是机器生成的。这项研究揭示了3D基因组结构和基因活动如何在成长中的小鼠大脑中发生变化. 这些动态对于神经发育和脑细胞类型至关重要.
科学领域
- 神经科学
- 基因组学
- 发育生物学
背景情况
- 三维基因组结构和基因转录对于哺乳动物的神经发育及其相关疾病至关重要.
- 然而,大脑中的单细胞3D基因组结构及其出生后的发育动态在很大程度上仍未被探索.
研究的目的
- 在单细胞分辨率下创建小鼠大脑转录组和3D基因组结构的综合图谱.
- 研究出生后早期基因表达和3D基因组组织的动态变化.
主要方法
- 使用基于循环的高分辨率多重回火和放大周期用于数字转录组学 (MALBAC-DT) 转录组分析.
- 用于高分辨率的3D基因组结构映射的双倍染色体构造捕获 (Dip-C).
- 开发了先进的多基因分析管道,以整合转录基因和表观基因数据.
主要成果
- 从正在发育的小鼠皮质和海马体生成了3,517个转录组和3,646个3D基因组结构的单细胞地图.
- 证明3D基因组结构类型与成年大脑中的细胞类型和基因表达 (A/B区) 相相关.
- 在出生后的第一个月内发现了转录组和3D基因组的广泛变化,神经元的3D基因组重新连接与基因表达模块.
- 观察到印记基因的等位基因特异性结构,显示本地和染色体范围的变异.
结论
- 这项研究为哺乳动物神经发育过程中转录组和3D基因组的单细胞动态提供了前所未有的见解.
- 这些发现突显了3D基因组组织在细胞类型的定义及其在发育过程中的动态重新连接中的关键作用.
- 发现神经发育中以前未知的调节层,由基因组架构控制.
相关概念视频
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 synthesis of 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 correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
In most mammals, females have two X chromosomes (XX) while males have an X and a Y chromosome (XY). The X chromosome contains significantly more genes than the Y chromosome. Therefore, to prevent an excess of X chromosome-linked gene expression in females, one of the two X chromosomes is randomly silenced during early development....
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...