Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there a...

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Veröffentlicht in:Nature communications 2023-07, Vol.14 (1), p.4071-4071, Article 4071
Hauptverfasser: Klein, Fabian, Veiga-Villauriz, Clara, Börsch, Anastasiya, Maio, Stefano, Palmer, Sam, Dhalla, Fatima, Handel, Adam E., Zuklys, Saulius, Calvo-Asensio, Irene, Musette, Lucas, Deadman, Mary E., White, Andrea J., Lucas, Beth, Anderson, Graham, Holländer, Georg A.
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Sprache:eng
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Zusammenfassung:The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells’ RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes. T cell development requires functionally diverse thymic epithelial cell (TEC) populations performing specific functions. Here, using massively parallel flow cytometry and machine learning, the authors examine in mice the TEC compartment from the perinatal period to adulthood, identify novel phenotypic markers and characterize the function of perinatal cortical TEC.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-39722-9