Opportunities for Single‐Cell Sequencing in Synthetic Biology

Abstract

Single-cell sequencing describes the ability to extract information from a single cell among a heterogeneous mix of cell types by sequencing its DNA or RNA. The development of this technology created tremendous excitement in biology. Akin to gaining higher resolution on a microscope, single-cell sequencing opened our eyes towards previously unknown cellular heterogeneity and the underlying molecular mechanisms. This technology, however, could in principle be applied to any nonliving particle capable of carrying nucleotides. This article proposes the application of single-cell sequencing in synthetic biology in order to analyze large numbers of artificiallygenerated or re-engineered synthetic cells simultaneously. The high-throughput nature of this technology provides the opportunity to test multiple hypotheses in parallel and thus accelerate the pace of discovery. Synthetic biology serves as a particularly exciting example of many overlooked non-canonical applications of single-cell sequencing.

Characterization of RNA content in individual phase-separated coacervate microdroplets

“…Taken together, our data demonstrate that single cell RNA sequencing technology is not confined to the analysis of living cells but also applicable to RNA characterization of in-vitro phase separated coacervates 18 . It allows for highly multiplexed analysis of multiple condensate types and has the potential to uncover many aspects of the role of RNA in condensate formation with implications on several scientific disciplines from chemistry to cell biology.…”

Characterization of RNA content in individual phase-separated coacervate microdroplets

“…Taken together, our data demonstrate that single-cell RNA sequencing technology is not confined to the analysis of living cells but also applicable to RNA characterization of in vitro phase-separated coacervates 43 . It allows for highly multiplexed analysis of multiple condensate types and has the potential to uncover many aspects of the role of RNA in condensate formation with implications on several scientific disciplines from chemistry to cell biology.…”