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Status |
Public on Dec 30, 2021 |
Title |
Zinc finger protein Zfp335 controls thymocyte differentiation and survival through b-selection-dependent and -independent mechanisms |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
T cell development proceeds in a series of developmental stages, which is precisely orchestrated by multiple signaling and molecular networks. Here we found a zinc finger protein Zfp335 intrinsically controls DN to DP transition, as T cell-specific deficiency in Zfp335 leads to a substantial accumulation of DN3 along with reduction of DP, CD4+ and CD8+ thymocytes. This developmental blockade at DN stage results from the impaired intracellular TCRβ expression as well as increased susceptibility to apoptosis in thymocytes. Transcriptomic and ChIP-seq analyses revealed a direct regulation of transcription factors Bcl6 and Rorc by Zfp335. Importantly, enhanced expression of TCRβ and Bcl6/RorγT restores the developmental defect during DN3 to DN4 transition and improves thymocytes survival, respectively. These findings identify a critical role of Zfp335 in controlling T cell development by maintaining intracellular TCR expression-mediated β-selection and independently activating cell survival signaling.
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Overall design |
Examination of DN4 thymocytes from the thymus of WT and Zfp335 deficient mice
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Contributor(s) |
Zhang B, Wang X, Jiao A, Su Y |
Citation(s) |
35113015 |
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Submission date |
Sep 21, 2021 |
Last update date |
Mar 03, 2022 |
Contact name |
昕 王 |
E-mail(s) |
wangxin928@stu.xjtu.edu.cn
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Phone |
+8615029001862
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Organization name |
xi'an jiaotong university
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Street address |
yanta west road 76
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City |
xi'an |
ZIP/Postal code |
710000 |
Country |
China |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA764931 |
SRA |
SRP338082 |