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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

Si-scRNA-seq: Enabling ambient-stable single-cell transcriptomics through spatially confined biosilicification

5 affiliations
  1. 1Guangdong Engineering Research Center of Low-Carbon Synthetic Biotechnology, State Key Laboratory of Pulp and Paper Engineering, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, People’s Republic of China
  2. 2National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People’s Republic of China
  3. 3Guangzhou National Laboratory, Guangzhou 510005, People’s Republic of China
  4. 4Center for Micro-Engineered Materials and the Department of Chemical and Biological Engineering, The University of New Mexico, Albuquerque, NM 87131
  5. 5Institute of Emergent Elastomers, School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, Guangdong, People’s Republic of China

Abstract

Single-cell RNA sequencing (scRNA-seq) is constrained by rapid RNA degradation during sample storage, necessitating cold-chain logistics. Here we present spatially confined biosilicification (SCB), wherein RNA is encapsulated within a nanoscopic layer of amorphous silicon dioxide, as a highly effective methodology enabling ambient-temperature preservation of single-cell transcriptomes. By judiciously incorporating a silicification inhibitor, SCB achieves spatiotemporal control over both intra- and extracellular silica deposition, preventing excessive crosslinking and cell aggregation while preserving RNA biointegrity and accessibility. scRNA-seq performed with biosilicified cells (Si-scRNA-seq) maintained high transcriptomic fidelity with fresh samples (R2 = 0.95 after 7 d) extending RNA half-life to 54.8 d at 25 °C, a 685-fold improvement compared to unprotected samples. Furthermore, Si-scRNA-seq confers robust resistance against oxidative and UV degradation. Compatible with mainstream platforms at ~0.1 RMB per sample, Si-scRNA-seq successfully resolves cellular heterogeneity in clinical lung, liver, and ovarian cancer specimens after extended room-temperature storage. Si-scRNA-seq provides a scalable and cold-chain–free solution for single-cell transcriptomics in research and clinical settings.

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BibTeX
@article{zhou2026siscrnaseq,
  title = {{Si-scRNA-seq: Enabling ambient-stable single-cell transcriptomics through spatially confined biosilicification}},
  author = {Liang Zhou and Ting Ruan and Ying He and Guangting Xie and Jingyu Qi and Xiaobao Cao and C. Jeffrey Brinker and Ya Liu and Wei Zhu},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2617730123},
  url = {https://doi.org/10.1073/pnas.2617730123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Si-scRNA-seq: Enabling ambient-stable single-cell transcriptomics through spatially confined biosilicification
AU  - Liang Zhou
AU  - Ting Ruan
AU  - Ying He
AU  - Guangting Xie
AU  - Jingyu Qi
AU  - Xiaobao Cao
AU  - C. Jeffrey Brinker
AU  - Ya Liu
AU  - Wei Zhu
PY  - 2026
DA  - 2026/10/23
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2617730123
UR  - https://doi.org/10.1073/pnas.2617730123
AB  - Single-cell RNA sequencing (scRNA-seq) is constrained by rapid RNA degradation during sample storage, necessitating cold-chain logistics. Here we present spatially confined biosilicification (SCB), wherein RNA is encapsulated within a nanoscopic layer of amorphous silicon dioxide, as a highly effective methodology enabling ambient-temperature preservation of single-cell transcriptomes. By judiciously incorporating a silicification inhibitor, SCB achieves spatiotemporal control over both intra- and extracellular silica deposition, preventing excessive crosslinking and cell aggregation while preserving RNA biointegrity and accessibility. scRNA-seq performed with biosilicified cells (Si-scRNA-seq) maintained high transcriptomic fidelity with fresh samples (R2 = 0.95 after 7 d) extending RNA half-life to 54.8 d at 25 °C, a 685-fold improvement compared to unprotected samples. Furthermore, Si-scRNA-seq confers robust resistance against oxidative and UV degradation. Compatible with mainstream platforms at ~0.1 RMB per sample, Si-scRNA-seq successfully resolves cellular heterogeneity in clinical lung, liver, and ovarian cancer specimens after extended room-temperature storage. Si-scRNA-seq provides a scalable and cold-chain–free solution for single-cell transcriptomics in research and clinical settings.
SN  - 0027-8424
SN  - 1091-6490
ER  -