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Effect of GRP75 deficiency on gene expression in DN3 thymocytes

ABSTRACT: Effect of GRP75 deficiency on gene expression in DN3 thymocytes

PROVIDER: PRJNA1115108 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29142255_1.fastq.gz	Fastqsanger.gz
	SRR29142255_2.fastq.gz	Fastqsanger.gz
	SRR29142256_1.fastq.gz	Fastqsanger.gz
	SRR29142256_2.fastq.gz	Fastqsanger.gz
	SRR29142257_1.fastq.gz	Fastqsanger.gz

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Effect of GRP75 deficiency on gene expression in DN3 thymocytes

Project description:Mitochondria and endoplasmic reticulum contacts (MERCs) regulate multiple cellular processes including cell survival and differentiation. Based on the observations that MERCs were specifically enriched in the CD4-CD8- double negative (DN) stage, we studied their role in early thymocyte development. We found that T-cell-specific knockout of Hspa9, which encodes GRP75, a chaperone mediates MERC formation by assembling the IP3R-GRP75-VDAC complex, impaired DN3 thymocyte viability and resulted in thymocyte developmental arrest at the DN3-DN4 transition. Mechanistically, GRP75 deficiency induced mitochondrial stress, releasing mitochondrial DNA (mtDNA) into the cytosol and triggering the type I interferon (IFN-I) response. IFN-I pathway contributed to both the impairment of cell survival and DN3-DN4 transition blockage, while increased lipid peroxidation (LPO) played a major role downstream of IFN-I. Thus, our study reveals the essential role of GRP75-dependent MERCs in early thymocyte development and uncovers the governing facts of cellular survival and differentiation in the DN stage.

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Miz-1 is required to coordinate the pre-TCR-dependent transitional step in DN3/DN4 thymocytes

Project description:Lineage negative, CD44 negative, CD25 positive thymocytes were isolated from wt mice or Miz1 POZ-domain knockout mice to analyze the effect of loss of Miz1 in the DN3 population of T-cells We used the mouse Affymetrix MOE430-2 microarray to characterize global gene expression changes of DN3 thymocytes from Miz1 knockout mice. We performed microarray based gene expression profiling to determine the effect of loss of Miz1 activity on the gene expression pattern of mouse DN3 thymocytes from wt and Miz1-delta-POZ mice.

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Effect of Ndrg3-deficiency on gene expression by CD8SP thymocytes

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Expression data from WT DN3, TCF-1-deficient DN3 thymocytes, and T cell lymphomas in TCF-1-deficient animals.

Project description:TCF-1 is an HMG family transcription factor which is known to be critical for T cell development. We discovered that it has a unique role in suppressing malignant transformation of developing thymocytes at early stages. We identified ID2 and LEF-1 as key TCF-1 target genens in tumor suppression. We used microarrays to detect gene expression changes in WT and TCF-1 deficient DN3 thymocytes as well as T cell lymphoma cells developed in TCF-1 KO mice. DN3 thymocytes were directly sorted from WT or TCF-1 KO mice. T cell lymphoma blast cells were also sorted from TCF-1 KO mice that developed the disease. RNA was extracted and hybridized to GeneChip Mouse GENE 1.0 ST arrays (Affymetrix).

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