Wolff Robert, Balzani Edoardo, Gelli Elisa, Polito Alessia, Serani Angelo, Tucci Valter
Genetics and Epigenetics of Behavior Laboratory, Fondazione Istituto Italiano di Tecnologia (IIT), Genoa, Italy.
Center for Computational Neuroscience, Flatiron Institute, Simons Foundation, New York, NY, USA.
Commun Biol. 2025 Jun 4;8(1):857. doi: 10.1038/s42003-025-08128-2.
Monoallelic gene expression is a pivotal phenomenon in developmental biology, notably through the influence of imprinted genes. Our model predicts that monoallelic expression generates expression variability, which we assess by measuring genetic noise and entropy within Shannon's information theory framework. Analyzing single-cell allele-specific expression across human and mouse datasets, we consistently observe increased expression variability due to monoallelic expression, affecting both imprinted and co-expressed non-imprinted genes. Moreover, we find decreasing variability in developing neurons and increasing variability in glial cells. The discovery of distinct noise patterns in over 80% of analyzed genes between glial and neuronal populations highlights the importance of differential noise in neurodevelopmental processes. Given the critical role of imprinted genes in biological processes such as growth and brain development, disruptions in their expression might contribute to various disorders. Understanding the stochastic nature of monoallelic expression and its genome-wide impact offers new insights into the mechanisms underlying these pathologies.
单等位基因表达是发育生物学中的一个关键现象，特别是通过印记基因的影响。我们的模型预测，单等位基因表达会产生表达变异性，我们通过在香农信息论框架内测量遗传噪声和熵来评估这种变异性。分析人类和小鼠数据集中的单细胞等位基因特异性表达，我们一致观察到由于单等位基因表达导致的表达变异性增加，这影响了印记基因和共表达的非印记基因。此外，我们发现发育中的神经元变异性降低，而胶质细胞变异性增加。在超过80%的分析基因中，胶质细胞和神经元群体之间存在明显的噪声模式差异，这凸显了差异噪声在神经发育过程中的重要性。鉴于印记基因在生长和大脑发育等生物学过程中的关键作用，其表达的破坏可能导致各种疾病。了解单等位基因表达的随机性本质及其全基因组影响，为这些病理学的潜在机制提供了新的见解。
