Single-cell genomics is a fast growing, emerging approach in which genomic technologies are applied at the level of single cells, rather than an entire population of cells.
Ever since Robert Hooke discovered the first cell in the 17th Century, scientists have been looking to better understand this basic unit of life. Despite the rapid evolution of genomic technologies over the past decade, the ability to interrogate the genomics of a single cell remained very challenging. Historically, many scientists believed that groups of very “similar” cells would have limited genomic variation, supporting the use of a cell population approach. However, recent single-cell genomic experiments have demonstrated that even seemingly identical cells can have significant genomic variations. These variations can play a critical role in human health and disease (Figure).
Over the past few years, there has been an explosion of single-cell genomics publications (growing at more than 40% per year. The segments of microbiology, basic cell biology, and stem cell biology represented the majority of these publications. Single-cell approaches have been enabling for microbiologists given that microbes, particularly novel microbes, can be challenging to culture to a sufficient population size to conduct traditional population-level genomic approaches. The emergence of single-cell genomics has enabled microbiologists to identify and analyze individual microbes at the genomic level.
Interestingly, single-cell genomics has also been adopted by traditional cell biologists interested in complementing their existing cell biology approaches (e.g., flow cytometry, patch clamp) with genomic analysis.
For stem cell biologists, single-cell genomics is a disruptive technology to better understand cell programming and differentiation. In the last few years, there has been an emergence of publications in specific disease areas, especially oncology, neurology, and immunology in which single-cell genomics has enabled an understanding of intrapopulation heterogeneity (e.g., tumor cell heterogeneity) and rare subpopulations (e.g., CD34+ and CD133+ hematopoietic stem cells).
Conducting single-cell genomics experiments has been challenging given that it requires the manual integration of a number of workflow steps, historically conducted by different research subspecialties, creating a “cross-functional skill gap.”
In step one, single cells must be isolated from bodily fluids or tissue, typically using technologies such as flow cytometry, laser capture microdissection, or micromanipulation. These technologies have been historically under the purview of cell biologists, not geneticists. Next, isolated single cells must be managed into separate compartments (so that their DNA/RNA does not mix) and then the DNA/RNA of each single cell needs to be amplified for downstream genomic analysis. (Current genomic analysis technologies are typically not sensitive enough to work with DNA/RNA from a single cell without amplification). Finally, during the third step the DNA/RNA is analyzed using genomic technologies such as qPCR or sequencing. The latter two steps are typically under the purview of geneticists, not cell biologists.
The combination of a lack of a system to integrate all steps of this workflow and the existence of a cross-functional skill gap among scientists has significantly limited the adoption of single-cell genomics to date.
The good news is that the single-cell genomics workflow is rapidly improving through integration of steps, optimized single-cell reagents, and higher throughput.
Most notably, Fluidigm has launched the C1™ Single-Cell Auto Prep System, which integrates cell isolation and sample prep into one instrument with the ability to integrate downstream with its BioMark™ HD qPCR platform for gene expression analysis. This represents the first end-to-end solution for single-cell qPCR and has the capacity to conduct analysis on 96 individual cells at a time.
Nanostring offers a protocol to conduct gene expression on single cells in suspension, thus integrating steps two and three. Additionally, other companies have launched reagents optimized for genomic amplification of single cells (e.g., Nugen’s Ovation® One-Direct System).
Similar to qPCR in the 1990s, all the right drivers are in place—high scientific interest, rapidly growing number of publications, optimized instruments and reagents—to really “unlock” the single-cell genomics market.
As a result, DeciBio believes that this market has reached an inflection point and will experience rapid growth over the next five or so years, with many segments growing at greater than 40% annually. DeciBio’s recently published “Single Cell Genomics (SCG): Market Size, Segmentation, Growth, Competition and Trends” market report provides detailed information about this rapidly growing market, highlighting some segments that are expected to more than double in size each year for the next three years.