Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada.
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
Transl Psychiatry. 2022 Aug 10;12(1):326. doi: 10.1038/s41398-022-02076-9.
Early life stress (ELS) induces long-term phenotypic adaptations that contribute to increased vulnerability to a host of neuropsychiatric disorders. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, are a proposed link between environmental stressors, alterations in gene expression, and phenotypes. Epigenetic modifications play a primary role in shaping functional differences between cell types and can be modified by environmental perturbations, especially in early development. Together with contributions from genetic variation, epigenetic mechanisms orchestrate patterns of gene expression within specific cell types that contribute to phenotypic variation between individuals. To date, many studies have provided insights into epigenetic changes resulting from ELS. However, most of these studies have examined heterogenous brain tissue, despite evidence of cell-type-specific epigenetic modifications in phenotypes associated with ELS. In this review, we focus on rodent and human studies that have examined epigenetic modifications induced by ELS in select cell types isolated from the brain or associated with genes that have cell-type-restricted expression in neurons, microglia, astrocytes, and oligodendrocytes. Although significant challenges remain, future studies using these approaches can enable important mechanistic insight into the role of epigenetic variation in the effects of ELS on brain function.
早期生活压力（ELS）会导致长期的表型适应，从而增加患多种神经精神疾病的易感性。表观遗传机制，包括 DNA 甲基化、组蛋白修饰和非编码 RNA，是环境应激源、基因表达改变和表型之间的一个被提出的联系。表观遗传修饰在塑造细胞类型之间的功能差异方面起着主要作用，并且可以通过环境干扰进行修饰，尤其是在早期发育过程中。与遗传变异的贡献一起，表观遗传机制协调特定细胞类型内的基因表达模式，从而导致个体之间的表型变异。迄今为止，许多研究已经提供了对 ELS 引起的表观遗传变化的深入了解。然而，尽管在与 ELS 相关的表型中存在细胞类型特异性的表观遗传修饰的证据，但这些研究中的大多数都检查了异质的脑组织。在这篇综述中，我们重点介绍了在从大脑中分离出来的特定细胞类型或与神经元、小胶质细胞、星形胶质细胞和少突胶质细胞中具有细胞类型特异性表达的基因相关的细胞类型中，ELS 诱导的表观遗传修饰的啮齿动物和人类研究。尽管仍然存在重大挑战，但使用这些方法的未来研究可以为表观遗传变异在 ELS 对大脑功能影响中的作用提供重要的机制见解。
