Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78870 |
| _version_ | 1818018313358278656 |
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| author | Tongcui Ma Matthew McGregor Leila Giron Guorui Xie Ashley F George Mohamed Abdel-Mohsen Nadia R Roan |
| author_facet | Tongcui Ma Matthew McGregor Leila Giron Guorui Xie Ashley F George Mohamed Abdel-Mohsen Nadia R Roan |
| author_sort | Tongcui Ma |
| collection | DOAJ |
| description | High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at the single-cell level. We implemented CyTOF-Lec to compare glycan features between different immune subsets from blood and multiple tissue compartments, and to characterize HIV-infected cell cultures. Using bioinformatics approaches to distinguish preferential infection of cellular subsets from viral-induced remodeling, we demonstrate that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection. Sialic acid levels were found to distinguish memory CD4+ T cell subsets expressing different amounts of viral entry receptors, pro-survival factors, homing receptors, and activation markers, and to play a direct role in memory CD4+ T cells’ susceptibility to HIV infection. The ability of sialic acid to distinguish memory CD4+ T cells with different susceptibilities to HIV infection was experimentally validated through sorting experiments. Together, these results suggest that HIV remodels not only cellular proteins but also glycans, and that glycan expression can differentiate memory CD4+ T cells with vastly different susceptibility to HIV infection. |
| first_indexed | 2024-04-14T07:37:18Z |
| format | Article |
| id | doaj.art-11ad9b2293b548ec8928b0045a349672 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:37:18Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-11ad9b2293b548ec8928b0045a3496722022-12-22T02:05:38ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.78870Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIVTongcui Ma0Matthew McGregor1Leila Giron2Guorui Xie3Ashley F George4Mohamed Abdel-Mohsen5https://orcid.org/0000-0002-9945-4314Nadia R Roan6https://orcid.org/0000-0002-5464-1976Department of Urology, University of California, San Francisco, San Francisco, United States; Gladstone Institutes, San Francisco, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, United States; Gladstone Institutes, San Francisco, United StatesThe Wistar Institute, Philadelphia, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, United States; Gladstone Institutes, San Francisco, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, United States; Gladstone Institutes, San Francisco, United StatesThe Wistar Institute, Philadelphia, United StatesDepartment of Urology, University of California, San Francisco, San Francisco, United States; Gladstone Institutes, San Francisco, United StatesHigh-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at the single-cell level. We implemented CyTOF-Lec to compare glycan features between different immune subsets from blood and multiple tissue compartments, and to characterize HIV-infected cell cultures. Using bioinformatics approaches to distinguish preferential infection of cellular subsets from viral-induced remodeling, we demonstrate that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection. Sialic acid levels were found to distinguish memory CD4+ T cell subsets expressing different amounts of viral entry receptors, pro-survival factors, homing receptors, and activation markers, and to play a direct role in memory CD4+ T cells’ susceptibility to HIV infection. The ability of sialic acid to distinguish memory CD4+ T cells with different susceptibilities to HIV infection was experimentally validated through sorting experiments. Together, these results suggest that HIV remodels not only cellular proteins but also glycans, and that glycan expression can differentiate memory CD4+ T cells with vastly different susceptibility to HIV infection.https://elifesciences.org/articles/78870CyTOFglycansHIVT cellslectinssialic acid |
| spellingShingle | Tongcui Ma Matthew McGregor Leila Giron Guorui Xie Ashley F George Mohamed Abdel-Mohsen Nadia R Roan Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV eLife CyTOF glycans HIV T cells lectins sialic acid |
| title | Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV |
| title_full | Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV |
| title_fullStr | Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV |
| title_full_unstemmed | Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV |
| title_short | Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV |
| title_sort | single cell glycomics analysis by cytof lec reveals glycan features defining cells differentially susceptible to hiv |
| topic | CyTOF glycans HIV T cells lectins sialic acid |
| url | https://elifesciences.org/articles/78870 |
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