人类大脑中的单细胞DNA甲基化和3D基因组结构
Wei Tian1, Jingtian Zhou1,2, Anna Bartlett1
1Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
概括
研究人员绘制了人类大脑细胞表观基因组, 确定了188种细胞类型及其分子特征. 这本地图书揭示了细胞类型的基因调节,并使用DNA甲基化模式来预测大脑细胞类型.
科学领域:
- 神经科学
- 基因组学
- 表观遗传学
背景情况:
- 了解人类大脑中的基因调节对于破译大脑功能和神经疾病至关重要.
- 之前的研究缺乏全面地绘制成年人大脑中的细胞类型特异性表观遗传特征的分辨率.
研究的目的:
- 创建一个高分辨率的多模式表观基因图谱,
- 描述不同类型的大脑细胞的分子特征和基因调节程序.
- 使用表观遗传学数据开发细胞类型识别的新方法.
主要方法:
- 来自三个成年男性大脑的46个区域的517,000多个细胞的单细胞DNA甲基化和染色质构成.
- 根据分子特征识别和描述188种不同的脑细胞类型.
- 对DNA甲基化,染色体可访问性,染色体组织和基因表达数据的综合分析.
- 开发单细胞甲基化条形码用于细胞类型预测.
主要成果:
- 188种人类大脑细胞类型的详细分子签名.
- 在细胞类型,皮质区域和基底中观察到一致的表观遗传和基因表达变化.
- 成功开发能够可靠地预测大脑细胞类型的甲基化条形码.
- 建立一个多模式的表观遗传脑细胞图谱.
结论:
- 这项研究为成年人大脑的细胞类型特异性基因调控提供了前所未有的洞察力.
- 开发的甲基化条形码为识别脑细胞类型提供了强大的工具.
- 这本表观基因图谱作为未来神经科学研究和理解大脑疾病的基础资源.
相关概念视频
Chromatin Packaging
15.4K
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...
15.4K
Inheritance of Chromatin Structures
6.3K
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...
6.3K
Genomic DNA in Eukaryotes
47.0K
Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.
47.0K
Epigenetic Regulation
3.0K
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...
X-chromosome...
3.0K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
The Nucleosome
1.7K
Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
1.7K


