Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801.
Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801.
Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2119891119. doi: 10.1073/pnas.2119891119. Epub 2022 Mar 2.
Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through C-enriched diets. A C magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient C-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.
神经元和遗传机制共同调节大脑功能。虽然有很多出色的方法可以在体内研究神经元活动，但目前还没有非破坏性的方法来测量活体大脑中的整体基因表达。在这里，我们提出了一种方法，即表观遗传磁共振成像（eMRI），它通过直接成像 DNA 甲基化（一种主要的基因表达调控因子）来克服这一限制。eMRI 利用蛋氨酸代谢途径通过富含 C 的饮食来标记基因组 DNA。然后，一种 C 磁共振波谱成像方法可以绘制标记 DNA 的空间分布。我们使用猪对 eMRI 进行了验证，猪的大脑在体积和解剖结构上与啮齿动物相比与人类更为相似，并且证实了大脑 DNA 的高效 C 标记。我们还发现了全脑 DNA 甲基化的强烈区域差异。就像针对区域神经元活动的功能磁共振成像测量对神经科学产生了变革性的影响一样，我们预计 eMRI 信号，既可以作为区域表观遗传活性的度量，也可以作为区域基因表达的可能替代指标，将能够促进对人类大脑功能、行为和疾病的许多新的研究。
