加州大学Päivi Pajukanta小组的一项最新研究开发出人皮下脂肪组织单细胞DNA甲基组和三维基因组图谱。2025年8月20日出版的《自然—遗传学》发表了这项成果。

该研究组阐明了以snm3C-seq为主题的SAT细胞类型的表观基因组景观。该课题组发现，SAT CG甲基化（mCG）在髓细胞中表现出明显的高甲基化，在脂肪细胞、脂肪干细胞和祖细胞中表现出低甲基化，驱动了705063个差异甲基化区域（DMRs）的近一半。

此外，TET1和DNMT3A被鉴定为细胞型水平mCG谱的可移植调节因子。全球mCG谱和染色体区隔化都反映了SAT细胞类型谱系。值得注意的是，脂肪细胞表现出更多的短程染色体相互作用，形成复杂的局部3D基因组结构，调节转录功能，包括脂肪生成。

此外，脂肪细胞DMRs和A区室在腹部肥胖全基因组关联研究（GWAS）变异和多基因风险中富集，而髓细胞A区室在炎症中富集。总之，该研究组描述了SAT单细胞水平的表观基因组景观，并将GWAS变异和腹部肥胖和炎症的分割多基因风险与SAT表观基因组联系起来。

据了解，人类皮下脂肪组织（SAT）的细胞类型水平的表观基因组景观尚未很好地表征。

附：英文原文

Title: Single-cell DNA methylome and 3D genome atlas of human subcutaneous adipose tissue

Author: Chen, Zeyuan Johnson, Das, Sankha Subhra, Kar, Asha, Lee, Seung Hyuk T., Abuhanna, Kevin D., Alvarez, Marcus, Sukhatme, Mihir G., Wang, Zitian, Gelev, Kyla Z., Heffel, Matthew G., Zhang, Yi, Avram, Oren, Rahmani, Elior, Sankararaman, Sriram, Laakso, Markku, Heinonen, Sini, Peltoniemi, Hilkka, Halperin, Eran, Pietilinen, Kirsi H., Luo, Chongyuan, Pajukanta, Pivi

Issue&Volume: 2025-08-20

Abstract: The cell-type-level epigenomic landscape of human subcutaneous adipose tissue (SAT) is not well characterized. Here, we elucidate the epigenomic landscape across SAT cell types using snm3C-seq. We find that SAT CG methylation (mCG) displays pronounced hypermethylation in myeloid cells and hypomethylation in adipocytes and adipose stem and progenitor cells, driving nearly half of the 705,063 differentially methylated regions (DMRs). Moreover, TET1 and DNMT3A are identified as plausible regulators of the cell-type-level mCG profiles. Both global mCG profiles and chromosomal compartmentalization reflect SAT cell-type lineage. Notably, adipocytes display more short-range chromosomal interactions, forming complex local 3D genomic structures that regulate transcriptional functions, including adipogenesis. Furthermore, adipocyte DMRs and A compartments are enriched for abdominal obesity genome-wide association study (GWAS) variants and polygenic risk, while myeloid A compartments are enriched for inflammation. Together, we characterize the SAT single-cell-level epigenomic landscape and link GWAS variants and partitioned polygenic risk of abdominal obesity and inflammation to the SAT epigenome.

DOI: 10.1038/s41588-025-02300-4

Source: https://www.nature.com/articles/s41588-025-02300-4