Quick Look
Spatial transcriptomics is a game-changer in genomics. Some cool technologies like MERFISH and FISSEQ have laid the groundwork. In 2019, Fei Chen, Sam Rodriques, and Evan Macosko at the Broad Institute came up with Slide-seq. This tech doesn’t require much more than a sequencer and offers sharp resolution with its tiny barcoded beads.
Right after they published their paper, they got bombarded with requests from other labs. Chen felt overwhelmed but was eager to put this tool in more hands. He wanted it to be used widely, but selling it as a product was tricky. Venture capitalists weren’t on board with selling it directly to researchers.
When the pandemic hit, Slide-seq got stuck in the lab, though Chen’s group kept improving it. Then in early 2021, Fei Chen had a chance meeting with Steve Fodor, co-founder of Affymetrix. They clicked, and along with Ari Chaney and Christina Fan, they formed Curio Bioscience.
By 2023, Curio Bioscience launched Seeker, the evolved version of Slide-seq. It comes as a kit with eight Seeker tiles, reagents, and data files for bead barcodes and spatial locations. Chen now believes the tech is mature and the timing perfect as the excitement for spatial transcriptomics has grown.
There are other similar spatial methods, like the highest resolution Stereo-seq by BGI-Research and 10X Genomics’s Visium. Stereo-Seq needs an MGI sequencer and is not available commercially yet, while Visium is the popular go-to spatial tech.
Slide-seq and now Seeker serve researchers in single-cell biology, tumor microenvironments, and developmental biology. It’s also beneficial for those working with non-traditional model organisms. I caught up with some scientists to hear their thoughts:
Diving into Uncharted Waters
Researchers like Anoja Perera from the Stowers Institute for Medical Research love Seeker for its versatility. Working on a variety of organisms, they switched entirely to Seeker from Slide-seq and 10X Genomics Visium. She shared with me how easy it was to transition to Seeker and the flexibility it offers. Their samples ranged from zebrafish to planaria.
Her small concern lies in whether Curio can keep up with production. Spatial technologies require a strong histology and molecular biology team, and labs new to spatial methods might need more training from Curio.
Angela Pisco at the Chan Zuckerberg Biohub leads a project on building a reference atlas using single cells. She’s been incorporating spatial data since 2021 and recently started using Seeker. Unlike some platforms, Seeker doesn’t work with formalin-fixed samples, and there’s no tissue image capture, making comparisons tricky. But Pisco values its high signal-to-noise ratio.
Even in the absence of imaging, the potential in spatial transcriptomics remains thrilling.
The Only Way Forward
Kelvin Chen of Osaka University, who focuses on immunology, used to find other spatial technologies either low in resolution or too pricey. Without knowing Chen, Macosko, or Rodriques, his introduction to Seeker came through Curio’s director of business development. Now utilizing Seeker, he highlights its ease of use for someone experienced with library prep.
Despite some difficulties in histology and tile size, the high resolution offered by Seeker sometimes overwhelmed their computational resources. Overall, Chen’s enthusiasm for its potential is evident.
Fei Chen eagerly awaits to see how others will use Seeker. He looks forward to directing more requests to Curio and plans to keep innovating in his lab.
Key Features
- Technology: Slide-seq has evolved to Seeker.
- Developers: Fei Chen, Sam Rodriques, and Evan Macosko from the Broad Institute.
- Launch: 2023 by Curio Bioscience.
- Application: Fits single-cell studies, tumor biology, developmental biology, and non-model organisms.
- Resolution: High, with precise barcoded beads.
- Other Technologies: Stereo-seq and 10X Genomics Visium.
Sample Workflow
- Preparation: Researchers start with fresh frozen samples.
- Reagents: Use provided kits and bead barcodes.
- Sequencing: Feed it into a sequencer.
- Analysis: Data includes spatial location info.
Advantages
- Broad application to various organisms.
- Flexibility in samples.
- High-resolution data.
Challenges
- No support for formalin-fixed samples.
- Lack of morphological image capture.
Spatial transcriptomics is still pushing boundaries and evolving. With Seeker now available, it holds exciting potential for pushing the limits of what we know about the spatial context of gene expression.
High-Precision Tools
- Bead Barcodes: For precise spatial location info.
- Seeker Tiles: Small tiles but high in detail.
These tools make it easier to explore tissue biology at an unmatched level of resolution. Scientists can now see the spatial context like never before.
Overcoming Hurdles
- Histology: Critical for success.
- Training: Needed for labs new to spatial methods.
As Seeker continues to develop, further improvements and adjustments will likely address existing limitations.
I can’t wait to see how this technology will unfold and what new discoveries it will lead to. From cancer to developmental biology, the sky’s the limit with spatial transcriptomics.
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