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Transcriptome analysis of acute graft-versus-host disease in children

ABSTRACT: Transcriptome analysis of acute graft-versus-host disease in children

PROVIDER: PRJNA706045 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13834377.fastq.gz	Fastqsanger.gz
	SRR13834378.fastq.gz	Fastqsanger.gz
	SRR13834379.fastq.gz	Fastqsanger.gz
	SRR13834380.fastq.gz	Fastqsanger.gz
	SRR13834381.fastq.gz	Fastqsanger.gz

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Acute graft-versus-host disease (gene expression profiling)

Project description:Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for high-risk hematological malignancies, yet a major complication associated with this therapy is acute graft-versus-host disease (GVHD). Despite a well-defined pathophysiological mechanism, there are no definitive markers for predicting acute GVHD development or progression to advanced stages. In the current study, we enrolled four acute GVHD and four acute GVHD-free recipients of allogeneic HSCT and collected peripheral blood just prior to onset of clinical acute GVHD for analysis on Affymetrix GeneChip Human Genome U133 Plus 2.0 microarrays. We noted significant differences in expression of 1,658 genes between control and acute GVHD patients, based on an analysis of covariance (ANCOVA) by type of transplant, a pooled error estimate, and a false discovery rate (FDR) of 10%. In conclusion, we offer the first report of a preliminary molecular signature of acute GVHD in allogeneic HSCT patients.

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Transcriptome analysis of acute graft-versus-host disease in children

Project description:Steroid-refractory gastrointestinal graft-versus-host disease (GI GVHD) is a major barrier to successful hematopoietic stem cell transplant (HSCT). Poor understanding of the pathophysiology of GI GVHD contributes to continued poor outcomes and high mortality rates. We therefore obtained rectosigmoidal mucosal biopsies from post-HSCT patients with GI GVHD and submitted them to RNA-sequencing in order to transcriptomally characterize GI GVHD. These were compared to patients undergoing endoscopy for routine clinical indications. Using single end, 50bp reads processed using Kallisto using genome annotations from Gencode v24 with transcripts per million as the output. We included 14,239 trancsripts in our analysis, where we compared GVHD vs non-GVHD with significance defined as FDR<0.05 and FC 1.5 using R package DESeq2. We identified 164 key genes, of which 141 were upregulated in GVHD, and were ontologically related to microbial response, key immune effectors, and cell migration/chemotaxis. Down-regulated genes were related to nutrient metabolism. Additionally, we performed WGCNA that highlighted ERK as a key upregulated pathway in GI GVHD.

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CD8+ T cell response in the Act-mOVA/OT-I model of acute graft versus host disease

Project description:Lethally irradiated C57Bl/6 Act-mOVA mice receiving allogeneic hematopoietic stem cell transplantation (aHSCT) from C57Bl/6 OT-I animals develop acute graft versus host disease (aGvHD) in a CD8+ T cell-dependent, reproducible manner, and succumb to the disease within 4-7 days. Tracking of UBC-GFP/OT-I graft CD8+ T cells discloses heavy infiltration of the GI tract, liver and lungs at the onset of the disease, and hallmark histologic features of acute gastrointestinal and hepatic GvHD, and aGVHD-associated lymphocytic bronchitis. This dataset describes gene expression patterns of CD45.1/OT-1 CD8+ T cells retrieved from the graft before (aHSCT + Day 0), and from various target organs of the host after (aHSCT + Day 4) grafting them into Act-mOVA recipients.

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Project description:To assess if gene expression signatures could predict acute graft-versus-host disease, we examined the global gene expression profiles of peripheral blood mononuclear cells at day +14 post-transplantation from 94 patients undergoing allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

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Project description:Defining TCF1+ progenitor allogeneic CD8 T cell subset in acute graft-versus-host disease

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