Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics.

IF 13 1区生物学 Q1 CELL BIOLOGY

Cell Discovery Pub Date : 2025-01-21 DOI:10.1038/s41421-025-00770-8

Honggui Wu, Maoxu Wang, Yinghui Zheng, X Sunney Xie

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引用次数: 0

Abstract

Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its transcriptome co-assay (dscHi-C-multiome) using droplet microfluidics. Using dscHi-C, we investigate chromatin structural changes during mouse brain aging by profiling 32,777 single cells across three developmental stages (3 months, 12 months, and 23 months), yielding a median of 78,220 unique contacts. Our results show that genes with significant structural changes are enriched in pathways related to metabolic process and morphology change in neurons, and innate immune response in glial cells, highlighting the role of 3D genome organization in physiological brain aging. Furthermore, our multi-omics joint assay, dscHi-C-multiome, enables precise cell type identification in the adult mouse brain and uncovers the intricate relationship between genome architecture and gene expression. Collectively, we developed the sensitive, high-throughput dscHi-C and its multi-omics derivative, dscHi-C-multiome, demonstrating their potential for large-scale cell atlas studies in development and disease.

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基于微滴的单细胞高通量三维基因组结构定位与同步转录组学。

单细胞三维（3D）基因组技术提高了我们对复杂组织中细胞类型特异性染色质结构的理解，但目前的方法在细胞通量方面受到限制。在这里，我们介绍了一种高通量单细胞Hi-C （dscHi-C）方法及其转录组联合测定（dscHi-C-多组）。利用dscHi-C，我们通过分析32,777个单细胞在三个发育阶段（3个月、12个月和23个月）的染色质结构变化，研究了小鼠大脑衰老过程中的染色质结构变化，得出了78,220个独特的接触值。我们的研究结果表明，具有显著结构变化的基因在神经元的代谢过程和形态变化以及神经胶质细胞的先天免疫反应相关通路中富集，突出了3D基因组组织在脑生理性衰老中的作用。此外，我们的多组学联合分析，dscHi-C-multiome，能够在成年小鼠大脑中精确识别细胞类型，并揭示基因组结构和基因表达之间的复杂关系。总之，我们开发了敏感的、高通量的dscHi-C及其多组学衍生物dscHi-C-multiome，展示了它们在发育和疾病的大规模细胞图谱研究中的潜力。

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

Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

24.20

自引率

0.60%

发文量

120

审稿时长

20 weeks

期刊介绍： Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.