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使用DNA甲基化配置文件量化人类皮层中不同细胞类型的比例
Eilis Hannon1, Emma L Dempster2, Jonathan P Davies2
1Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, RILD Building, Royal Devon & Exeter Hospital, Barrack Road, Exeter, Devon, EX2 5DW, UK. E.J.Hannon@exeter.ac.uk.
BMC biology
|January 25, 2024
概括
新的计算模型使用DNA甲基化数据准确估计人类皮质细胞比例. 质细胞的数量是神经元细胞的两倍,特定的细胞类型比例与阿尔茨海默氏症神经病理学有关.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 人类皮质细胞组成在个体之间有所不同,因此需要在使用批量组织的表观基因组范围关联研究 (EWAS) 中包含共变量.
- 从DNA甲基化数据中估计细胞比例的计算方法至关重要,因为实验细胞计数的频繁不可用.
研究的目的:
- 验证和描述一个扩展的参考DNA甲基化数据集,用于量化人类皮质细胞组成.
- 评估结合神经元和质细胞亚型的新型解模型的性能.
主要方法:
- 测试了八个参考面板,其中包括不同类型的神经元和质细胞组合.
- 使用计算重建和经验推导的人类皮质DNA甲基化数据来表征解卷性能.
主要成果:
- 新型大脑解密模型准确地估计了出生后人类皮质样本中的细胞比例,但不是在产前皮质或小脑中.
- 人类皮质中的质细胞的数量是神经元细胞的两倍.
- 在阿尔茨海默氏症神经病理和特定细胞类型比例之间发现了显著的关联,包括减少的NeuNeg/SOX10Neg和增加的NeuNeg/SOX10Pos核.
结论:
- 新的解卷模型为人类皮质提供了准确的细胞比例估计.
- 这些模型作为一个社区资源,用于控制脑皮层组织使用大脑疾病的表观遗传研究的细胞异质性.
相关概念视频
00:58Genomic DNA in Eukaryotes
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.
00:58DNA Packaging
Overview
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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?
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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 structures.
03:17Inheritance of Chromatin Structures
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 DNA...
01:32Chromatin Packaging
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
01:20Genetic Material
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