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The scMuscle database provides another important piece of information that single sequencing experiments fail to produce - spatial data that details how cells organize and interact across the tissue landscape. "Now we have a comprehensive picture of the very rare cell types that we know are involved in skeletal muscle repair, but weren't previously sampled." It assembles into a richer and more complicated painting," Cosgrove said. "We liken it to creating a mosaic with multiple artists. They combined 88 publicly available datasets with several of their own, leading to the scMuscle database, which houses the transcriptomic data from approximately 365,000 cells involved in muscle injury over a wide range of ages and experimental conditions. So, they used advanced computational techniques to start merging collections to paint the fuller picture. The Cornell team knew there were other large sequencing datasets being developed, each capturing their own share of data. "We just couldn't collect enough data ourselves to paint the whole picture of these subtle transitions as cells mature and specialize." "Imagine if you had a paint-by-numbers picture and you only colored in a quarter of the numbers," said Cosgrove, who co-led the development of scMuscle along with De Vlaminck and doctoral student David McKellar.
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But of those cells, fewer than 200 of them were committed or fusing myogenic cells - the rare transient states that sequencing struggles to document. It's a problem that Cosgrove ran into when he published a 2020 cell atlas containing 35,000 individual cells involved in the repair process. Recent advances in single-cell RNA sequencing allow biologists to identify tens of thousands of cells from a single tissue sample, but because muscle stem cells account for less than 1% of those cells - with their short-lived transient cell offspring being even more rare - sequencing experiments simply can't capture the complete picture of muscle regeneration.
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Co-senior authors are Ben Cosgrove and Iwijn De Vlaminck, both associate professors of biomedical engineering in the College of Engineering. 12 in the journal Communications Biology. Biologists have struggled to study rare and transient muscle cells involved in the process, but Cornell engineers have lifted the curtain on these elusive dynamics with the launch of scMuscle, one of the largest single-cell databases of its kind.Ī report on the work was published Nov.