Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1263152 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33580512_1.fastq.gz | Fastqsanger.gz | |||
| SRR33580512_2.fastq.gz | Fastqsanger.gz | |||
| SRR33580513_1.fastq.gz | Fastqsanger.gz | |||
| SRR33580513_2.fastq.gz | Fastqsanger.gz | |||
| SRR33580514_1.fastq.gz | Fastqsanger.gz |
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Project description:<p><strong>BACKGROUND:</strong> Hematopoietic stem cell transplantation is a curative procedure for a variety of conditions. Despite major advances, a plethora of adverse clinical outcomes can develop post-transplantation including graft-versus-host disease and infections, which remain the major causes of morbidity and mortality. There is increasing evidence that the gastrointestinal microbiota is associated with clinical outcomes post-hematopoietic stem cell transplantation. Herein, we investigated the longitudinal dynamics of the gut microbiota and metabolome and potential associations to clinical outcomes in pediatric hematopoietic stem cell transplantation at a single centre.</p><p><strong>RESULTS:</strong> On admission (baseline), the majority of patients presented with a different gut microbial composition in comparison to healthy control children with a significantly lower alpha diversity. A further, marked decrease in alpha diversity was observed immediately post-transplantation and in most microbial diversity, and composition did not return to baseline status while hospitalized. Longitudinal trajectories identified continuous fluctuations in microbial composition, with the dominance of a single taxon in a significant proportion of patients. Using pam clustering, three clusters were observed in the dataset. Cluster 1 was common pre-transplantation, characterized by a higher abundance of <em>Clostridium XIVa</em>, <em>Bacteroides</em> and <em>Lachnospiraceae</em>; cluster 2 and cluster 3 were more common post-transplantation with higher abundance of <em>Streptococcus</em> and <em>Staphylococcus</em> in the former whilst <em>Enterococcus</em>, <em>Enterobacteriaceae</em> and <em>Escherichia</em> predominated in the latter. Cluster 3 was also associated with a higher risk of viraemia. Likewise, further multivariate analysis reveals <em>Enterobacteriaceae</em>, viraemia, use of total parenteral nutrition and various antimicrobials contributing towards cluster 3, <em>Streptococcaceae</em>, <em>Staphylococcaceae</em>, <em>Neisseriaceae</em>, vancomycin and metronidazole contributing towards cluster 2. <em>Lachnospiraceae</em>, <em>Ruminococcaceae</em>, <em>Bifidobacteriaceae</em> and not being on total parenteral nutrition contributed to cluster 1. Untargeted metabolomic analyses revealed changes that paralleled fluctuations in microbiota composition; importantly, low fecal butyrate was associated with higher risk of viraemia.</p><p><strong>CONCLUSIONS:</strong> These findings highlight the frequent shifts and dominations in the gut microbiota of pediatric patients undergoing hematopoietic stem cell transplantation. The study reveals associations between the fecal microbiota, metabolome and viraemia. To identify and explore the potential of microbial biomarkers that may predict risk of complications post-HSCT, larger multi-centre studies investigating longitudinal microbial profiling in pediatric hematopoietic stem cell transplantation are warranted.</p>
2022-05-11 | MTBLS4065 | MetaboLights
Project description:The mechanisms underlying operational tolerance after hematopoietic stem cell transplantation in humans are poorly understood. We studied two independent cohorts of patients who underwent allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-identical siblings. Primary tolerance was associated with long-lasting reshaping of the recipients' immune system compared to their healthy donors with an increased proportion of regulatory T cell subsets and decreased T cell activation, proliferation, and migration. Transcriptomics profiles also identified a role for nicotinamide adenine dinucleotide biosynthesis in the regulation of immune cell functions. We then compared individuals with operational tolerance and nontolerant recipients at the phenotypic, transcriptomic, and metabolomic level. We observed alterations centered on CD38<sup>+</sup>-activated T and B cells in nontolerant patients. In tolerant patients, cell subsets with regulatory functions were prominent. RNA sequencing analyses highlighted modifications in the tolerant patients' transcriptomic profiles, particularly with overexpression of the ectoenzyme <i>NT5E</i> (encoding CD73), which could counterbalance CD38 enzymatic functions by producing adenosine. Further, metabolomic analyses suggested a central role of androgens in establishing operational tolerance. These data were confirmed using an integrative approach to evaluating the immune landscape associated with operational tolerance. Thus, balance between a CD38-activated immune state and CD73-related production of adenosine may be a key regulator of operational tolerance.
2021-12-22 | MTBLS221 | MetaboLights
Project description:The mechanisms underlying operational tolerance after hematopoietic stem cell transplantation in humans are poorly understood. We studied two independent cohorts of patients who underwent allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-identical siblings. Primary tolerance was associated with long-lasting reshaping of the recipients' immune system compared to their healthy donors with an increased proportion of regulatory T cell subsets and decreased T cell activation, proliferation, and migration. Transcriptomics profiles also identified a role for nicotinamide adenine dinucleotide biosynthesis in the regulation of immune cell functions. We then compared individuals with operational tolerance and nontolerant recipients at the phenotypic, transcriptomic, and metabolomic level. We observed alterations centered on CD38<sup>+</sup>-activated T and B cells in nontolerant patients. In tolerant patients, cell subsets with regulatory functions were prominent. RNA sequencing analyses highlighted modifications in the tolerant patients' transcriptomic profiles, particularly with overexpression of the ectoenzyme <i>NT5E</i> (encoding CD73), which could counterbalance CD38 enzymatic functions by producing adenosine. Further, metabolomic analyses suggested a central role of androgens in establishing operational tolerance. These data were confirmed using an integrative approach to evaluating the immune landscape associated with operational tolerance. Thus, balance between a CD38-activated immune state and CD73-related production of adenosine may be a key regulator of operational tolerance.
2021-12-22 | MTBLS220 | MetaboLights
Project description:To study the role of the receptor Neo1 in Hematopoietic stem cells (HSC) we transplanted Neo1 deficient bone marrow and wildtype controls on a CD45.2 background into lethally irradiated CD45.1 recipients. Either 4 or 15 months after transplantation we isolated HSC (Lineage -, Sca-1+, c-Kit+, Cd150+, CD48-, CD34-, CD45.2+) to identify molecular differences due to Neo1 deficiency and found a loss of HSC quiescence and signatures associated with decreased stem cell function.
2020-07-22 | E-MTAB-7902 | biostudies-arrayexpress
Project description:Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production1, 2. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division3-8. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a role for chaperone-mediated autophagy (CMA)9, a selective form of lysosomal protein degradation, in sustaining adult HSC function. CMA is required for stem cell protein quality control and upregulation of fatty acid metabolism upon HSC activation. We identify that CMA activity decreases with age in HSC and show that genetic or pharmacological activation of CMA can restore functionality of old HSC. Together, our findings provide mechanistic insights into a new role for CMA in sustaining quality control, appropriate energetics and overall long-term hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation.
2021-03-05 | PXD022196 | Pride
Project description:The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation. Two centers data was included, which are 41 samples from Stanford as the training set and 44 samples from UCLA as the test set. 26 samples from Stanford and 15 samples from UCLA were used in microarray Agilent whole human genome microarray
2012-02-01 | E-GEOD-30886 | biostudies-arrayexpress
Project description:The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation.
2012-02-01 | GSE30886 | GEO
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Project description:To clarify the mechanism through which HEMGN (also known as EDAG in human) controls the survival and functions of hematopoietic stem and progenitor cells (HSPCs) under transplantation stress, we compared the transcriptome of Hemgn-/- and WT HSPCs isolated from primary recipients 6h after transplantation by RNA sequencing (RNA-Seq).
2021-11-22 | GSE146949 | GEO
Project description:Analysis of donor CD4+ and CD8+ T cells purified from spleens and ovaries after murine syngeneic and allogeneic hematopoietic stem cell transplantation Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). While the role of pretransplant conditioning regimen has been well appreciated, increasing application of reduced-intensity conditioning facilitated us to revisit the other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice. To study transcriptomes of donor T cells infiltrating into the ovary, donor T cells were sorted from recipients' ovaries and microarray analysis was performed.
2017-05-12 | GSE81397 | GEO