| Autor: |
Zoë Steier, Dominik A. Aylard, Laura L. McIntyre, Isabel Baldwin, Esther Jeong Yoon Kim, Lydia K. Lutes, Can Ergen, Tse-Shun Huang, Ellen A. Robey, Nir Yosef, Aaron Streets |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.07.12.452119 |
| Popis: |
The development of CD4 and CD8 T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-MHCI/II by the T cell antigen receptor (TCR) determines the lineage choice, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. We applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and lineage-restricted mice to generate a comprehensive timeline of cell state for each lineage. These analyses revealed a sequential process whereby all thymocytes initiate CD4 lineage differentiation during an initial wave of TCR signaling, followed by a second TCR signaling wave that coincides with CD8 lineage specification. CITE-seq and pharmaceutical inhibition experiments implicate a TCR/calcineurin/NFAT/GATA3 axis in driving the CD4 fate. Overall, our data suggest that multiple redundant mechanisms contribute to the accuracy and efficiency of the lineage choice. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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