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Defining TFAP4 transcriptional regulation in pre-leukemic Eμ-MYC pre-B lymphoma cells

ABSTRACT: Defining TFAP4 transcriptional regulation in pre-leukemic Eμ-MYC pre-B lymphoma cells

PROVIDER: PRJNA937164 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23563605_1.fastq.gz	Fastqsanger.gz
	SRR23563605_2.fastq.gz	Fastqsanger.gz
	SRR23563606_1.fastq.gz	Fastqsanger.gz
	SRR23563606_2.fastq.gz	Fastqsanger.gz
	SRR23563607_1.fastq.gz	Fastqsanger.gz

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Defining TFAP4 transcriptional regulation in pre-leukemic Eμ-MYC pre-B lymphoma cells

Project description:Many lymphoid malignancies arise from deregulated c-MYC expression in cooperation with additional genetic lesions. While many of these cooperative genetic lesions have been discovered and their functions characterised, DNA sequence data of primary patient samples suggest that many more do exist. However, the nature of their contributions to c-MYC driven lymphomagenesis have not yet been investigated. We identified TFAP4 as a potent suppressor of c-MYC driven lymphoma development in a previous genome-wide CRISPR knockout screen in primary cells in vivo. CRISPR deletion of TFAP4 in Eµ-MYC transgenic haematopoietic stem and progenitor cells (HSPCs) and transplantation of these manipulated HSPCs into lethally irradiated animals significantly accelerated c-MYC-driven lymphoma development. Interestingly, TFAP4 deficient Eµ-MYC lymphomas all arose at the pre-B cell stage of B cell development. This observation prompted us to characterise the transcriptional profile of pre-B cells from pre-leukaemic mice transplanted with Eµ-MYC/Cas9 HSPCs that had been transduced with sgRNAs targeting TFAP4. This analysis revealed that TFAP4 deletion reduced expression of several master regulators of B cell differentiation, such as Spi1, SpiB and Pax5, which are direct target genes of both TFAP4 and MYC. We therefore conclude that loss of TFAP4 leads to a block in differentiation during early B cell development, thereby accelerating c-MYC-driven lymphoma development.

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RIBO-seq analysis of YTHDF2-deficient pre-leukemic cells and control pre-leukemic cells

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Microarray data from YTHDF2-deficient pre-leukemic cells and control pre-leukemic cells

Project description:YTHDF2 is overexpressed in a broad spectrum of human acute myeloid leukemias (AML). To study the role of YTHDF2 in leukemia, c-Kit+ cells from foetal livers of Ythdf2fl/fl;Vav-iCre (Ythdf2CKO) and Ythdf2fl/fl (Ythdf2CTL) 14.5 dpc embryos were transduced with Meis1 and Hoxa9 oncogenes and serially re-plated to generate pre-leukemic cells. Total RNA from Ythdf2CKO (n=5) and Ythdf2CTL (n=5) pre-leukemic cells were used for Affymetrix global gene expression analysis.

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RIBO-seq analysis of YTHDF2-deficient pre-leukemic cells and control pre-leukemic cells

Project description:YTHDF2 is overexpressed in a broad spectrum of human acute myeloid leukemias (AML). To study the role of YTHDF2 on translation regulation in leukemia, c-Kit+ cells from foetal livers of Ythdf2fl/fl; Vav-iCre (Ythdf2CKO) and Ythdf2fl/fl (Ythdf2CTL) 14.5 dpc embryos were transduced with Meis1 and Hoxa9 oncogenes and serially re-plated to generate pre-leukemic cells. RIBO-seq libraries were then prepared from Ythdf2CKO (n=3) and Ythdf2CTL (n=3) pre-leukemic cells.

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