MIT pairs Raman spectra with single-cell sequencing on the same cells to barcode senescence

Both measurements came off the same cells. Raman microscopy shines near-infrared or visible light on a cell and reports its chemical composition without harming it ^[2]. RNA sequencing consumes the cell it reads ^[3]. Run the two techniques on separate populations and you have two descriptions with no link between them at the level of an individual cell. Run them on the same cells and each sequencing profile becomes a label for one optical signature, so the spectrum can stand in for the profile afterwards. The MIT group calls the paired signatures barcodes ^[4].

The samples were skin and lung tissue from 2-month-old and 26-month-old mice ^[6]. The older animals were thirteen times the age of the younger ones ^[8]. Two tissues test whether a signature travels beyond the one it was found in, and an increase in lipid synthesis, among the most dramatic changes the team saw, appeared in both lung and skin cells ^[7]. The sequencing was spatial, so a cell's position in the tissue sits alongside its expression levels and its spectrum ^[5].

"Our idea was to look at many different features to characterize senescence. That's why we wanted to combine both single-cell gene expression and Raman microscopy, so that we can characterize senescence from two complementary views," said Jian Shu, an assistant professor at Massachusetts General Hospital and Harvard Medical School and one of the paper's senior authors ^[13].

The state the barcode detects is not always harmful. Senescent cells play critical roles in embryonic development and tissue regeneration ^[14]. "Senescence is not just a pathological condition," said Peter So, director of MIT's Laser Biomedical Research Center and also a senior author ^[12].

The clinical version arrived as a hypothetical. "You can imagine that one day we may develop an endoscope that can look inside your body and identify cellular senescence," said Jeon Woong Kang, an MIT research scientist and a senior author ^[11]. The measurements in the paper were made in mouse cells, and the group is now working on adapting the method for human tissue ^[10].

Senescence itself is usually triggered by DNA damage and locks the cell cycle irreversibly, leaving cells that do not die but change shape, metabolism and gene expression ^[15]. The immune system normally clears them, and clears them less well with age; accumulation has been linked to sagging skin, muscle weakness, osteoarthritis and type 2 diabetes ^[16].

Whether a spectrum can substitute for a destructive assay depends on how often the barcode is wrong about cells it was not trained on. The account published by phys.org does not report that figure, or the number of mice and cells measured ^[19].