Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity
Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicit...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105774 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826212106229252096 |
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| author | Gaublomme, Jellert T. Yosef, Nir Lee, Youjin Gertner, Rona S. Yang, Li V. Wu, Chuan Pandolfi, Pier Paolo Mak, Tak Satija, Rahul Kuchroo, Vijay K. Park, Hongkun Regev, Aviv Shalek, Alexander K |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science Gaublomme, Jellert T. Yosef, Nir Lee, Youjin Gertner, Rona S. Yang, Li V. Wu, Chuan Pandolfi, Pier Paolo Mak, Tak Satija, Rahul Kuchroo, Vijay K. Park, Hongkun Regev, Aviv Shalek, Alexander K |
| author_sort | Gaublomme, Jellert T. |
| collection | MIT |
| description | Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and
pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or differentiated in vitro under either pathogenic or non-pathogenic polarization conditions. Computational analysis relates a spectrum
of cellular states in vivo to in vitro differentiated Th17 cells, and unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four new genes: Gpr65, Plzp, Toso and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17
function in autoimmunity, and can identify targets for selective suppression of pathogenic Th17 cells while potentially sparing non-pathogenic tissue-protective ones |
| first_indexed | 2024-09-23T15:16:29Z |
| format | Article |
| id | mit-1721.1/105774 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:16:29Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1057742022-10-02T01:52:27Z Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity Gaublomme, Jellert T. Yosef, Nir Lee, Youjin Gertner, Rona S. Yang, Li V. Wu, Chuan Pandolfi, Pier Paolo Mak, Tak Satija, Rahul Kuchroo, Vijay K. Park, Hongkun Regev, Aviv Shalek, Alexander K Institute for Medical Engineering and Science Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Regev, Aviv Shalek, Alexander K Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or differentiated in vitro under either pathogenic or non-pathogenic polarization conditions. Computational analysis relates a spectrum of cellular states in vivo to in vitro differentiated Th17 cells, and unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four new genes: Gpr65, Plzp, Toso and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity, and can identify targets for selective suppression of pathogenic Th17 cells while potentially sparing non-pathogenic tissue-protective ones National Institutes of Health (U.S.) (Grant P50 HG006193) National Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051) Klarman Cell Observatory 2016-12-09T16:25:38Z 2016-12-09T16:25:38Z 2015-11 2015-08 Article http://purl.org/eprint/type/JournalArticle 00928674 http://hdl.handle.net/1721.1/105774 Gaublomme, Jellert T. et al. “Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity.” Cell 163.6 (2015): 1400–1412. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1016/j.cell.2015.11.009 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Gaublomme, Jellert T. Yosef, Nir Lee, Youjin Gertner, Rona S. Yang, Li V. Wu, Chuan Pandolfi, Pier Paolo Mak, Tak Satija, Rahul Kuchroo, Vijay K. Park, Hongkun Regev, Aviv Shalek, Alexander K Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity |
| title | Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity |
| title_full | Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity |
| title_fullStr | Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity |
| title_full_unstemmed | Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity |
| title_short | Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity |
| title_sort | single cell genomics unveils critical regulators of th17 cell pathogenicity |
| url | http://hdl.handle.net/1721.1/105774 https://orcid.org/0000-0001-8567-2049 |
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