PAN’s MERSCOPE Platform Provides High-Resolution Spatial Transcriptomics for Stanford Researchers
By Sarah C.P. Williams | The Beckman Center News / Fall 2024
MERSCOPE run 2: Left lung sample 7101 overview.
To better understand lung maintenance and how it can progress to disease, postdoctoral fellow Laura Crowley, PhD, wants to know how different cell types in mouse and human lungs are arranged, and how these cells communicate and interact. To do this, she needs not only to take precise measurements of the genes being expressed in a variety of lung cells, but also to map that gene expression spatially, on a cell-by-cell basis.
“When you have single-cell resolution for spatial transcriptomics, you can begin to investigate how cells interact with each other,” says Dr. Crowley, a member of Mark A. Krasnow, M.D., PhD’s biochemistry lab. “You can confirm that a cell you think might be signaling to another cell is indeed physically next to it, and see the breadth of changes in gene expression that those specific cells might express compared to other cells of the same type.”
Thanks to the new MERSCOPE spatial transcriptomics technology that was recently added at the Protein and Nucleic Acid (PAN) Facility at the Beckman Center, Dr. Crowley and other researchers will now be able to dive even deeper into those kinds of investigations.
MERSCOPE .vzg file – zoom-in on cells with transcripts shown
Vizgen - Visualizer UI in analyzing output data
Advanced Research Requires Advanced Tools
The questions that Dr. Crowley is asking cannot be answered with standard single-cell RNA sequencing. That process involves digesting a tissue and mixing cells together before analyzing each cell—and in the process, losing information about where each cell came from. Early spatial transcriptomics technologies used various methods to maintain spatial information, but they often did not quite have single-cell resolution or had limited depth.
"A lot of people invested their resources into platforms that didn’t quite have cellular resolution,” says Dr. Crowley.
Now, that is changing. In collaboration with Dr. Crowley and Dr. Krasnow, the PAN Facility has added the Vizgen MERSCOPE spatial transcriptomics platform to its suite of research tools. The platform retains spatial information with sub-micron accuracy, and can detect up to approximately 1,000 custom-selected RNA transcripts, allowing researchers to detect the sub-cellular localization of a wide range of transcripts for a variety of purposes.
Funded by the Howard Hughes Medical Institute, the MERSCOPE platform will allow Dr. Crowley and other Stanford researchers to conduct high-resolution, single-cell spatial transcriptomics experiments.
Beckman Center Shared Resources Benefit Multiple Stanford Labs
In the past, many individual labs at Stanford invested in their own spatial transcriptomics platforms, but state-of-the-art technologies are often expensive and difficult for an individual lab to afford. Dr. Crowley and Dr. Krasnow knew that they wanted the best equipment possible—and that they didn’t have enough spatial transcriptomics experiments to fill every waking hour. So they approached Michael Eckart, PhD, director of the PAN Facility, about making the MERSCOPE a shared resource through the service center.
“Rather than just getting another private machine, we thought it would be ideal to have this open for others to use,” says Dr. Crowley. “And the PAN Facility is very flexible and easy to work with.”
Before deciding on the Vizgen MERSCOPE platform, Dr. Crowley carried out pilot experiments using mouse lung and brain tissue, testing several different spatial transcriptomics platforms. The Vizgen MERSCOPE, she says, performed the best, providing the highest-quality, highest-resolution data.
“Dr. Crowley was instrumental in obtaining the identical tissue samples, determining the gene panels to be used, and analyzing the subsequent data,” says Dr. Eckart. “It is critical to use real-world samples in comparing different instrument capabilities. The conclusion from the benchmarking study was that the Vizgen MERSCOPE technology met the criteria for implementation at PAN.”
Dr. Crowley says she is excited to begin collecting data on the new platform, as well as to see how others in the community use the resource. “This is a really good opportunity for collaboration,” she says. “We can work with other researchers who are also using this technology, so everyone learns from each other on optimal tissue prep and panel design.”
Already, Dr. Eckart’s staff at the PAN Facility have been trained to assist with the MERSCOPE technology and are ready to help researchers who want to use the new spatial transcriptomics platform.
“This is another example of a collaboration that leverages Beckman resources to benefit the entire Stanford scientific community,” says Dr. Eckart.
Scientists who are interested in working with the MERSCOPE spatial transcriptomics technology should contact Dr. Eckart at meckart@stanford.edu.
For more information (media inquiries only), contact:
Naomi Love
(650) 723-7184
naomi.love@stanford.edu
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