Sequential-GAM constructs the single-cell geometric 3D genome structure

doi:10.1093/nar/gkag794

2026-08-14

DOI：10.1093/nar/gkag794

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染色质的3D结构对细胞身份和基因调控至关重要。然而，全基因组范围内的层次几何结构在单细胞中的组织方式仍不明确。本文开发了Sequential-GAM（序列基因组架构图谱）方法，通过捕捉连续的核薄片来构建层次几何结构，并估计了单细胞中染色体、区室、亚区室和基因的径向位置。我们发现，包括组蛋白修饰和亚区室在内的多种表观基因组特征，从核中心到核周呈现径向梯度。此外，我们估计了层次结构的变异，揭示了亚区室B1和B2的动态径向位置。进一步，我们定义了准稳定拓扑关联域集（q-stable TADs），其中TADs彼此间保持相对稳定的距离。有趣的是，q-stable TADs揭示了染色质结构稳定性与转录活性的相关性。最后，我们发现单细胞中基因的径向距离及其径向位置稳定性与其表达水平呈负相关。综上所述，Sequential-GAM能够估计单细胞中3D基因组的几何结构，并揭示结构稳定性和细胞间异质性。

期刊

Nucleic Acids Research

IF:

13.1

论文数:

3.6W

被引数:

29.0W

机构

Tsinghua University

学者数:

4.9K

论文数: 1.8K

被引数: 0

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