Epigenome profiling identifies H3K27me3 regulation of extracellular matrix composition in human corticogenesis.

IF 15 1区医学 Q1 NEUROSCIENCES

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-22 DOI:10.1016/j.neuron.2025.06.016

Nora Ditzer, Ezgi Senoglu, Annika Kolodziejczyk, Theresa M Schütze, Aikaterina Nikolaidi, Karolin Küster, Katrin Sameith, Sevina Dietz, Razvan P Derihaci, Cahit Birdir, Anne Eugster, Mike O Karl, Andreas Dahl, Pauline Wimberger, Franziska Baenke, Claudia Peitzsch, Mareike Albert

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引用次数: 0

Abstract

Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodeling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass-cytometry-based approach for the simultaneous single-cell analysis of more than 30 epigenetic marks. We identify Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 as the modification with the strongest cell-type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation toward differentiation. Cell-type-specific profiling of H3K27me3 identified neuronal differentiation and extracellular matrix (ECM) genes in the human neocortex. PRC2 inhibition resulted in increased production of the ECM proteins Syndecan 1 and laminin alpha 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.

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表观基因组分析鉴定H3K27me3调控人类皮质发生中的细胞外基质组成。

表观遗传机制调节神经发生过程中的基因表达程序，但人类皮层发育过程中表观遗传重塑的程度仍不清楚。在这里，我们通过利用Epi-CyTOF来描述人类发育中的新皮层的表观遗传景观，Epi-CyTOF是一种基于大规模细胞计量的方法，可同时对30多个表观遗传标记进行单细胞分析。我们发现Polycomb suppression complex 2 （PRC2）介导的H3K27me3是具有最强细胞类型特异性富集的修饰。抑制人皮质类器官PRC2可导致神经祖细胞（NPC）增殖向分化方向转变。H3K27me3的细胞类型特异性分析鉴定了人类新皮层中的神经元分化和细胞外基质（ECM）基因。PRC2抑制导致ECM蛋白Syndecan 1和层粘连蛋白α 1的产生增加。总的来说，本研究全面表征了特定神经细胞类型的表观遗传状态，并强调了H3K27me3在调节人类发育中的新皮层ECM组成中的新作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuron 医学-神经科学

CiteScore

24.50

自引率

3.10%

发文量

382

审稿时长

1 months

期刊介绍： Established as a highly influential journal in neuroscience, Neuron is widely relied upon in the field. The editors adopt interdisciplinary strategies, integrating biophysical, cellular, developmental, and molecular approaches alongside a systems approach to sensory, motor, and higher-order cognitive functions. Serving as a premier intellectual forum, Neuron holds a prominent position in the entire neuroscience community.