Three Pillars of 10x: Outlook for Single Cell, Spatial and In Situ Platforms
By Allison Proffitt
January 11, 2023 | The 41st annual J.P. Morgan Healthcare Conference kicked off on Monday in San Francisco—in person again after two years of a virtual conference. Serge Saxonov, CEO and co-founder of 10x Genomics, kicked off Monday’s sessions with an overview of the company’s overall progress in its Visium, Chromium, and Xenium platforms. Instead of delving too deeply in specific product announcements, Saxonov emphasized the strength of the 10x team, the mergers and acquisitions that have led to the development of the platforms, and the breadth of the company offerings.
Unsurprisingly, Saxonov believes that 10x is on the leading edge of a tipping point in biology. While recent focuses have been on genomics, what he calls compiling a “parts list of human biology”, the next phase of research will expand to address downstream biological advances, multiomics, and more advanced work with cells, tissues, and organs, he argues.
The 10x Genomics offerings now include the three pillars Saxonov promised in 2020—the Chromium single cell sequencing platform, the Visium spatial genomics platform, and the Xenium in situ platform. He predicted that 10x platforms together will replace legacy toolkits across life sciences including bulk next-gen sequencing, PCR, ELISAs, Western blots, and more.
The Chromium single sequencing platform, launched in 2016, is the oldest 10x platform and “allows you to see what is happening in your samples at the right level of resolution: single cell resolution at the fundamental unit of biology,” Saxonov said. With more than 4,000 instruments sold, the platform is now central to an extensive ecosystem of users, datasets, protocols, and papers. The company is investing here, Saxonov said, to drive scale in terms of number of samples, reduce the total cost of the experiment, and remove logistical barriers to larger experiments.
The Visium spatial genomics platform, which 10x Genomics launched in 2019, allows researchers “to see where things are happening in your sample: how the molecules are arranged with respect to each other in tissue,” Saxonov says. “It gives you an unbiased analysis of the entire tissue, the entire transcriptome. As such, it really bridges the worlds of histology and molecular biology together.” He reported Visium’s use in thousands of labs and in more than 400 papers thus far.
In June 2022, 10x launched Visium CytAssist. The instrument addresses an important customer pain point with Visium, he said, letting them use standard histology slides and workflows. “It marries your typical standard glass slide with the tissue mounted on it with the special Visium slide and transfers the molecules from that tissue onto the Visium slide,” he explained, “greatly simplifying” workflows. Importantly, the development makes archived tissue samples already mounted on glass accessible to Visium scrutiny.
“It’s been met with great enthusiasm by our customers, and we see it as by far the best way to run Visium and is the future of the platform,” Saxonov emphasized.
The company is investing aggressively in the Visium platforms, he said, focusing on expanding tissue types, measuring more analytes, and adding more workflows. Saxonov did not, however, mention Visium HD, the single-cell resolution spatial transcriptomics product that he announced at the J.P. Morgan Healthcare Conference in January 2021. Visium HD was originally predicted to ship in the first half of 2022 and would offer visibility 400 times higher than the current Visium solution, he said at the time, based on “big, fundamental advances in the underlying microarray technology.”
When asked, during Q&A, for a specific update on Visium HD timing, Saxonov demurred. “We are very strongly committed [to this platform]. We’re working really hard, and when we’re ready to give an update, we will give an update for sure.”
As the final of the three pillars, Xenium is 10x’s platform for in situ analysis. The platform was born out of two 2020 acquisitions, and offers targeted spatial profiling of genes and proteins at subcellular resolution via Xenium Explorer, software for interactive data visualization. The company announced the first commercial shipment in early December 2022.
Xenium enables subcellular mapping of hundreds of RNA targets, generating high quality data with high sensitivity and specificity to reveal new insights into cellular structure and function.
“This is something that would have seemed like science fiction just a short while ago. It provides this incredibly detailed view of the tissues at subcellular resolution. But it is now a reality. Even more so, we built the system for routine use, fast turnaround time, to be a workhouse in labs around the world.”
The platform works with custom panels and is also compatible with standard pathology. The platform has “tons of headroom,” Saxonov said, and he said the company has an extensive roadmap for future capabilities for the platform, increasing throughput and flexibility, and offering advanced analysis, visualization, and deeper integration with digital pathology and morphology.
There are a lot of players and interest in the in situ market right now, and not yet a lot of clarity for customers, Saxonov admits. “We have full confidence in investing in innovation, investing in customer success, leveraging our three platforms,” he adds. “We intend to lead the way and make this platform as meaningful and important as what we’ve done with Chromium and beyond.”
Balancing the Three-Legged Stool
The three 10x platforms aim to resolve biology’s complexity, Saxonov said. He expects the company’s initial core customer base—genomics and technology-oriented researchers—will likely be “naturally disposed toward having all three because they can most naturally take advantage of all three platforms and can think of use cases most readily.”
As the company expands its customer base, Saxonov expects some “splintering” of spatial customers, who may be keen to work with tissues, but not go through the disassociation route. “We do think that spatial has a lot of potential to bring new customers into the fold,” he added.
But of equal concern to how many platforms one customer could support is the possibility of overlap among the three platforms. For instance, the moderator pointed out, both Chromium and Visium HD (when it’s released) should offer single cell and whole transcriptome capabilities.
The shakeout, Saxonov said, is still uncertain. It’s not fully clear how the market will respond. “There are some ways in which the Chromium approach is really, really attractive because it kind of allows you to achieve a census of your cell states in a very efficient way,” he said. “Especially if you want to go really deep in terms of profiling immune receptors or some other kind of really intricate features, Chromium can be really, really powerful and is likely to stay here for a long, long time as a work horse for those kinds of experiments.”
With the launch of Xenium, sales and marketing is another challenge, Saxonov said. 10x is being very intentional about balancing sales and marketing resources across the three platforms. “We’re balancing incentives, but at the same time we strongly believe the size of our commercial force is a big advantage. These three platforms oftentimes really go together, and going to a customer with a value proposition around one oftentimes helps to bring the other platform into the mix, into the conversation. We’re finding that consistently,” he said. “Our goal is to balance the three platforms appropriately, but also leverage the size of our salesforce and boost the synergy between the platforms to drive the sales of all three.”