4.7 Article

A flexible microfluidic system for single-cell transcriptome profiling elucidates phased transcriptional regulators of cell cycle

Journal

SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41598-021-86070-z

Keywords

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Funding

  1. Edmond Lily Safra fellowship
  2. Sir Henry Dale fellowship - Wellcome Trust [215454/Z/19/Z]
  3. Sir Henry Dale fellowship - Royal Society [215454/Z/19/Z]
  4. Wellcome Trust Seed award [205990/Z/17/Z]
  5. National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London
  6. Wellcome Trust [205990/Z/17/Z, 215454/Z/19/Z] Funding Source: Wellcome Trust

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The Nadia Instrument is a flexible, cost-effective, and user-friendly droplet-based microfluidics system capable of capturing a large number of single cells or nuclei's 3' mRNA in a single run. It demonstrates highly reproducible droplet size, low doublet rates, and high mRNA capture efficiency. When combined with different buffers and barcoded bead configurations, it enables diverse applications and the identification of distinct cell populations.
Single cell transcriptome profiling has emerged as a breakthrough technology for the high-resolution understanding of complex cellular systems. Here we report a flexible, cost-effective and user-friendly droplet-based microfluidics system, called the Nadia Instrument, that can allow 3 ' mRNA capture of similar to 50,000 single cells or individual nuclei in a single run. The precise pressure-based system demonstrates highly reproducible droplet size, low doublet rates and high mRNA capture efficiencies that compare favorably in the field. Moreover, when combined with the Nadia Innovate, the system can be transformed into an adaptable setup that enables use of different buffers and barcoded bead configurations to facilitate diverse applications. Finally, by 3 ' mRNA profiling asynchronous human and mouse cells at different phases of the cell cycle, we demonstrate the system's ability to readily distinguish distinct cell populations and infer underlying transcriptional regulatory networks. Notably this provided supportive evidence for multiple transcription factors that had little or no known link to the cell cycle (e.g. DRAP1, ZKSCAN1 and CEBPZ). In summary, the Nadia platform represents a promising and flexible technology for future transcriptomic studies, and other related applications, at cell resolution.

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