Single-cell spatial MIST for versatile, scalable detection of protein markers Journal Article
| Authors: | Meah, A.; Vedarethinam, V.; Bronstein, R.; Gujarati, N.; Jain, T.; Mallipattu, S. K.; Li, Y.; Wang, J. |
| Article Title: | Single-cell spatial MIST for versatile, scalable detection of protein markers |
| Abstract: | High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ tagging (MIST) transfers the spatial protein expression information to an ultrahigh-density, large-scale MIST array. This technique has been optimized to reach single-cell resolution by adoption of smaller array units and 30% 8-arm PEG polymer as transfer medium. Tissue cell nuclei stained with lamin B have been clearly visualized on the MIST arrays and are colocalized with detection of nine mouse brain markers. Pseudocells defined at 10 μm in size have been used to fully profile tissue regions including cells and the intercellular space. We showcased the versatility of our technology by successfully detecting 20 marker proteins in kidney samples with the addition of five minutes atop the duration of standard immunohistochemistry protocols. Spatial MIST is amenable to iterative staining and detection on the same tissue samples. When 25 proteins were co-detected on 1 mouse brain section for each round and 5 rounds were executed, an ultrahigh multiplexity of 125 proteins was obtained for each pseudocell. With its unique abilities, this single-cell spatial MIST technology has the potential to become an important method in advanced diagnosis of complex diseases. © 2023 by the authors. |
| Keywords: | immunohistochemistry; controlled study; nonhuman; proteins; biological marker; animal cell; mouse; cytology; animal tissue; animal experiment; proteomics; in situ hybridization; diagnosis; molecular biology; tissue; kidney transplantation; cells; single cell analysis; single-cell analysis; single cells; male; article; iterative methods; fast protein liquid chromatography; mouse brain; protein markers; single cells analysis; mist array; multiplex biosensor; spatial proteomics; multiplex in situ tagging array; spatial multiplex; spatial proteomic; multiplex in situ tagging |
| Journal Title: | Biosensors |
| Volume: | 13 |
| Issue: | 9 |
| ISSN: | 2079-6374 |
| Publisher: | MDPI |
| Date Published: | 2023-09-01 |
| Start Page: | 852 |
| Language: | English |
| DOI: | 10.3390/bios13090852 |
| PROVIDER: | scopus |
| PMCID: | PMC10526469 |
| PUBMED: | 37754086 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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