2. Academic Validation
  3. Semi-automated IT-scATAC-seq profiles cell-specific chromatin accessibility in differentiation and peripheral blood populations

Semi-automated IT-scATAC-seq profiles cell-specific chromatin accessibility in differentiation and peripheral blood populations

  • Nat Commun. 2025 Mar 17;16(1):2635. doi: 10.1038/s41467-025-57931-2.
Wei Jin # 1 2 3,  Jingchun Ma # 4,  Li Rong # 4,  Shengshuo Huang 4,  Tuo Li 5,  Guoxiang Jin 6,  Zhongjun Zhou 7 8 9
Affiliations

Affiliations

  • 1 Pediatric Research Institute, Dongguan Children Hospital, Guangdong Medical University, Dongguan, China. jinwei5@connect.hku.hk.
  • 2 Medical Research Centre; Guangdong Cardiovascular Institute; Key Laboratory for Immune and Genetic Research of Chronic Nephropathy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China. jinwei5@connect.hku.hk.
  • 3 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong. jinwei5@connect.hku.hk.
  • 4 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
  • 5 Department of Endocrinology, Changzheng Hospital, Shanghai, China.
  • 6 Medical Research Centre; Guangdong Cardiovascular Institute; Key Laboratory for Immune and Genetic Research of Chronic Nephropathy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
  • 7 Pediatric Research Institute, Dongguan Children Hospital, Guangdong Medical University, Dongguan, China. zhongjun@hku.hk.
  • 8 Medical Research Centre; Guangdong Cardiovascular Institute; Key Laboratory for Immune and Genetic Research of Chronic Nephropathy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China. zhongjun@hku.hk.
  • 9 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong. zhongjun@hku.hk.
  • # Contributed equally.
PMID: 40097444 DOI: 10.1038/s41467-025-57931-2
Abstract

Single-cell ATAC-seq (scATAC-seq) enables high-resolution mapping of chromatin accessibility but is often limited by throughput, cost, and equipment requirements. Here, we present indexed Tn5 tagmentation-based scATAC-seq (IT-scATAC-seq), a semi-automated, cost-effective, and scalable approach that leverages indexed Tn5 transposomes and a three-round barcoding strategy. This workflow prepares libraries for up to 10,000 cells in a single day, reduces the per-cell cost to approximately $0.01, and maintains high data quality. Comprehensive benchmarking demonstrates that IT-scATAC-seq achieves robust library complexity, high signal specificity, and improved cost-efficiency compared to existing methods. We apply IT-scATAC-seq to mouse embryonic stem cells, capturing chromatin remodelling during early differentiation, and to human peripheral blood mononuclear cells, resolving cell-type-specific regulatory programs. Here, we show that IT-scATAC-seq provides a robust and efficient approach for high-resolution single-cell epigenomic investigations, balancing scalability, data quality, and accessibility.

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