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Single-cell RNA sequencing analysis of blood B cells from human allogeneic hematopoietic transplant patients

ABSTRACT: Single-cell RNA sequencing analysis of blood B cells from human allogeneic hematopoietic transplant patients

PROVIDER: PRJNA677928 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR13041600.fastq.gz	Fastqsanger.gz
	SRR13041601.fastq.gz	Fastqsanger.gz
	SRR13041602.fastq.gz	Fastqsanger.gz
	SRR13041603.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing analysis of blood B cells from human allogeneic hematopoietic transplant patients

Project description:Single cell analysis of gene expression in blood B cells from allogeneic hematopoietic stem cell transpant (HCT) patients that either developed chronic GVHD, or never developed chronic GVHD.

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Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

Project description:The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

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NGS in hematopoietic cell transplant recipients

Project description:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pre-transplant genetic susceptibility is evident in adult TA-TMA patients at the level of TMA-associated variants and further investigated the association of genetic variants with clinical outcomes. We studied 30 patients with TA-TMA at a median of 73 (9-540) post-transplant days, donors of 18/30 patients and 30 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pre-transplant peripheral blood was analyzed by targeted next generation sequencing for complement regulatory genes and ADAMTS13. Donors presented significantly lower frequency of rare variants (p=0.049) and variants in exonic/splicing/UTR regions (p=0.025), compared to TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13 (p=0.001), CD46 (p=0.002), CFH (p=0.010) and CFI (p=0.031). Pathogenic variants were found in ADAMTS13, CFH, CFI and CFB, while homozygous pathogenic variants in ADAMTS13 and CFB were evident in only 4 TA-TMA patients (p=0.038). Patients refractory to conventional treatment (70%) were significantly (p=0.045) enriched for variants in exonic/splicing/UTR regions compared to responders. Nineteen of 30 patients (63%) succumbed to transplant-related mortality, which was also associated with significantly (p=0.012) increased frequency of variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pre-transplant genomic screening may be useful to intensify monitoring and early intervention in high-risk patients.

2019-04-18 | E-MTAB-7848 | biostudies-arrayexpress

Oral Samples (HOMIM-v.02); A Characterization of the Oral Microbiome in Allogeneic Stem Cell Transplant Patients

Project description:The purpose of this study is to describe the effects of allogeneic stem cell transplant on oral microbiota and to examine differences in those patients who acquired respiratory complications. Forty-five patients were consented for the study and followed for 100 days post-transplant. Eleven patients represented by 115 speciment had specimens collected before and after transplant were subjected to further analysis. The Human Oral Microbe Identification Microarray was used for this analysis. In these 11 patients, five developed respiraotry complications after transplant and six did not develop this complication. Cluster analysis was used to identify patterns in the data. 115 specimens are included from 11 patients. These specimens were collected before and after transplant. There are no duplicate samples.

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Oral Samples (HOMIM-v.02); A Characterization of the Oral Microbiome in Allogeneic Stem Cell Transplant Patients

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Transcription profiling of human CD34+ cells from bone marrow and G-CSF-mobilized peripheral blood to investigate why the latter are optimal for allogeneic transplant recipients

Project description:Comparison of gene expression in CD34+ cells from bone marrow and G-CSF-mobilized peripheral blood to investigate why the latter are optimal for allogeneic transplant recipients.

2008-06-13 | E-GEOD-500 | biostudies-arrayexpress

Profiling the blood compartment of Hematopoietic Stem Cell Transplant patients during Human Cytomegalovirus reactivation

Project description:Profiling the blood compartment of Hematopoietic Stem Cell Transplant patients during Human Cytomegalovirus reactivation

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Immune Escape after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with Acute Myeloid Leukemia

Project description:Although allogeneic hematopoietic cell transplantation (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of post-transplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape the graft-versus-leukemia effect, we evaluated immune signatures in bone marrow samples from four pediatric patients using a multimodal single-cell approach. Downregulation of MHC class II (MHC-II) expression observed at post-transplant relapse was most profound in progenitor-like blasts and was accompanied by correlative changes in transcriptional regulation. Dysfunction of activated NK cells and CD8+ T cell subsets at the time of relapse was evidenced by the loss of IFN-γ response, TNF-a signaling via NF-kB, and IL-2/STAT5 signaling. Clonotype analysis of post-transplant relapse samples revealed expansion of dysfunctional T cells and enrichment of T regulatory and T helper cells. Using novel computational methods, our results illustrate a diverse immune-related transcriptional signature in post-transplantation relapses not previously reported in pediatric AML.

2023-06-26 | GSE207104 | GEO

Tolerance associated gene expression following allogeneic hematopoietic cell transplantation

Project description:Biologic markers of immune tolerance may facilitate tailoring of immune suppression duration after allogeneic hematopoietic cell transplantation (HCT). In a cross-sectional study, peripheral blood samples were obtained from tolerant (n=15, median 38.5 months post-HCT) and non-tolerant (n=17, median 39.5 post-HCT) HCT recipients and healthy control subjects (n=10) for analysis of immune cell subsets and differential gene expression. There were no significant differences in immune subsets across groups. We identified 281 probe sets unique to the tolerant (TOL) group and 122 for non-tolerant (non-TOL). These were enriched for process networks including NK cell cytotoxicity, antigen presentation, lymphocyte proliferation, and cell cycle and apoptosis. Differential gene expression was enriched for CD56, CD66, and CD14 human lineage-specific gene expression. Differential expression of 20 probe sets between groups was sufficient to develop a classifier with > 90% accuracy, correctly classifying 14/15 TOL cases and 15/17 non-TOL cases. These data suggest that differential gene expression can be utilized to accurately classify tolerant patients following HCT. Prospective investigation of immune tolerance biologic markers is warranted. Samples were collected after allogeneic hematopoietic cell transplantation (HCT) or in healthy control subjects. Peripheral blood samples were obtained from tolerant (n=15, median 38.5 months post-HCT) and non-tolerant (n=17, median 39.5 post-HCT) HCT recipients and healthy control subjects (n=10).

2015-05-25 | E-GEOD-64300 | biostudies-arrayexpress

DNA Methylation Dynamics in Blood after Hematopoietic Cell Transplant

Project description:Classically, epigenetic deregulation is considered a common hallmark of cancer. Nevertheless, recent publications have demonstrated its association with a large array of human diseases such as autoimmune disorders and environmental factors such as diet. Despite the increasing relevance of DNA methylation for the study of critical biological processes and for the development of novel biomarkers, DNA methylation analysis applied to the study of hematopoietic cell transplantation (HCT) has not yet been explored. Here, we analyzed global DNA methylation in blood samples by using a pyrosequencing based methylation assay of repetitive DNA elements (LINE1 and NBL2) in a cohort of 47 patients with allogenic HCT up to 12 months post-HCT. We observed that the recipients stably maintained the donor’s global methylation levels after transplant. Nonetheless, NBL2 methylation is affected by physiopathological events such as development of mixed chimerism. Microarray-based DNA methylation analysis of promoters revealed that methylation in more than 200 genes is altered 1 month post-HCT when compared with non-pathological methylation levels in the donor’s blood. Interestingly, this number dramatically decreased by 6 months post-HCT. Finally, based in the microarray data, we analyzed by pyrosequencing DNA methylation in IFN-γ, FASL, and IL-10 and found a statistically significant association between methylation in these immune genes and the severity of the acute graft-versus-host disease. In conclusion, our results provide strong evidence that DNA methylation changes in blood are linked to underlying physiological events and demonstrate that DNA methylation analysis is a viable strategy for the study of hematopoietic cell transplantation and for development of biomarkers. Bisulphite converted DNA from 6 blood samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

2013-02-27 | E-GEOD-36832 | biostudies-arrayexpress

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