| Autor: |
Miaoran Xia, Bingbing Wang, Wujianan Sun, Dengyu Ji, Xuefeng Huang, Minghang Yu, Ziyang Su, Ping Chen, Kun Qu, Xi Wang |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1961347/v1 |
| Popis: |
Histone demethylase Lsd1 has been shown to play a critical role in hematopoietic differentiation. However, its physiological functions in thymocyte development remain elusive. We observed that the specific deletion of Lsd1 in thymocytes at the double-negative stage causes significant thymic atrophy and reduces peripheral T cells with impaired proliferation capacity. Single-cell RNA-sequencing (scRNA-seq) combined with strand-specific total RNA-seq and ChIP-seq analysis revealed that ablation of Lsd1 in T cell precursors led to the aberrant de-repression of endogenous retroelements (EREs), which then resulted in a viral mimicry state and activated the interferon pathway. Furthermore, deletion of Lsd1 blocked the programmed sequential down-regulation of CD8 expression at the DP→CD4+CD8lo stage and induced an innate-memory phenotype in both thymic and peripheral T cells. Overall, our study provides new insight into the function of Lsd1 as an important maintainer of ERE homeostasis in early T cell development. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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