Co-detection and sequencing of genes and transcripts from the same single cells facilitated by a microfluidics platform
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Despite the recent advance of single-cell gene expression analyses, co-measurement of both genomic and transcriptional signatures at the single-cell level has not been realized. However such analysis is necessary in order to accurately delineate how genetic information is transcribed, expressed, and regulated to give rise to an enormously diverse range of cell phenotypes. Here we report on a microfluidics-facilitated approach that allows for controlled separation of cytoplasmic and nuclear contents of a single cell followed by on-chip amplification of genomic DNA and cytoplasmic mRNA. When coupled with off-chip polymerase chain reaction, gel electrophoresis and Sanger sequencing, a panel of genes and transcripts from the same single cell can be co-detected and sequenced. This platform is potentially an enabling tool to permit multiple genomic measurements performed on the same single cells and opens new opportunities to tackle a range of fundamental biology questions including non-genetic cell-to-cell variability, epigenetic regulation, and stem cell fate control. It also helps address clinical challenges such as diagnosing intra-tumor heterogeneity and dissecting complex cellular immune responses.
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In 2014, a microfluidics-based approach achieved the first whole-genome and whole-transcriptome amplification and sequencing from one cell, allowing several genomic measurements.
“Overcoming these shortcomings, we reported the first amplification and sequencing of a whole genome and whole transcriptome from a single cell using a microfluidics-facilitated technology in 2014, which captured single cells using microvalve-based control channels, selectively lysed and separated cytoplasmic and nuclear contents, and then performed on-chip amplification, thereby enabling multiple”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [20]
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- Authors
- Han, L., Zi, X., Garmire, L. X., Wu, Y., Weissman, S. M., Pan, X., & Fan, R.
- Affiliations
- Yale University (US)
- Second Military Medical University (CN)
- Cancer Center of Hawaii (US)
- Yale Cancer Center (US)
- Corresponding author
- Weissman, Sherman M.
- Pan, Xinghua
- Fan, Rong
- Venue
- Scientific Reports
- Published
- 2014-09-26
- Volume
- 4
- Issue
- 1
- Pages
- 6485-6485
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4175731
- OpenAlex
- W1975120491
- Cited by
- 83
- References
- 50
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 13 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 8 · 2015: 4
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (1351443, U54 CA143798)
- Yale University
- National Institutes of Health (CA143798)
- National Cancer Institute (U54CA143798, CA143798)
- National Institute of General Medical Sciences (P01GM099130, P20GM103457)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
- Keywords
- single-cell genomics, single-cell transcriptomics, microfluidics, cell-to-cell variability, epigenetic regulation, stem cell fate, intratumoral heterogeneity, immune response
- MeSH terms
- DNA, Humans, RNA, Messenger, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Gene Expression Regulation, Neoplastic, Genomics, Microfluidics, Epigenesis, Genetic, Cell Line, Tumor, Single-Cell Analysis
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