Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA347635 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4413140.fastq.gz | Fastqsanger.gz | |||
| SRR4413150.fastq.gz | Fastqsanger.gz | |||
| SRR4413141.fastq.gz | Fastqsanger.gz | |||
| SRR4413142.fastq.gz | Fastqsanger.gz | |||
| SRR4413143.fastq.gz | Fastqsanger.gz |
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Project description:Recent pre-clinical and clinical evidences indicate that hematopoietic stem and progenitor cells (HSPCs) and/or their progeny can serve as vehicles for therapeutic molecule delivery across the blood brain barrier by contributing to the turnover of myeloid cell populations in the brain. However, the differentiation and functional characteristics of the cells reconstituted after transplantation are still to be determined, and in particular whether bona fide microglia could be reconstituted by the donor cell progeny post-transplant to be assessed. We here firstly demonstrate that HSPC transplantation can generate transcriptionally-dependable new microglia through a stepwise process reminiscent of physiological post-natal microglia maturation. Hematopoietic cells able to generate new microglia upon transplantation into myeloablated recipients are retained within human and murine long-term hematopoietic stem cells (HSCs). Similar transcriptionally dependable new microglia cells can also be generated by intra-cerebral ventricular delivery of HSPCs. Importantly, this novel route is associated to a clinically relevant faster and more widespread microglia replacement compared to systemic HSPC injection. Overall, this work supports the relevance and feasibility of employing HSPCs for renewing brain myeloid and microglia cells with new populations endowed with the ability to exert therapeutic effects in the central nervous system, and identifies novel modalities, such as transplantation of enriched stem cell fractions and direct brain delivery of HSPCs, for increasing the actual contribution of the transplanted cells to microgliosis and their therapeutic activity.
2017-12-09 | GSE87799 | GEO
Project description:This is a mathematical model describing the hematopoietic lineages with leukemia lineages, as controlled by end-product negative feedback inhibition. Variables include hematopoietic stem cells, progenitor cells, terminally differentiated HSCs, leukemia stem cells, and terminally differentiated leukemia stem cells.
2024-09-02 | BIOMD0000000898 | BioModels
Project description:The conditions supporting the generation of microglia-like cells in the central nervous system (CNS) after transplantation of hematopoietic stem/progenitor cells (HSPC) have been extensively studied to advance the treatment of neurodegenerative disorders. Here, we challenge the HSPC transplantation paradigm by exploring different cell subsets and delivery routes with the goal of favoring the establishment of a robust and exclusive engraftment of HSPCs and their progeny in the CNS of transplant recipients. In this setting, we show that the CNS environment uniquely drives the expansion, distribution and myeloid differentiation of the locally transplanted cells towards a microglia-like phenotype. Importantly, intra-CNS transplantation of engineered HSPCs benefit 5xFAD Alzheimer’s disease mice, a finding that provides not only the first example of efficacy of HSPC gene therapy in this indication, but also a proof of the therapeutic potential of this novel approach that determines a CNS-restricted engraftment of the transplant progeny cells.
2024-08-28 | GSE275808 | GEO
Project description:The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD).
The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.
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Project description:SET domain containing 2 (Setd2), encoding a histone methyltransferase, is associated with many hematopoietic diseases when mutated. By generating a novel exon 6 conditional knockout mouse model, we described an essential role of Setd2 in maintaining the adult hematopoietic stem cells. Loss of Setd2 results in leukopenia, anemia, and increased platelet accompanied with hypocellularity, erythroid dysplasia, and mild fibrosis in bone marrow. Setd2 knockout mice show significantly decreased hematopoietic stem and progenitor cells except for erythroid progenitors. Setd2 knockout hematopoietic stem cells fail to establish long-term bone marrow reconstitution after transplantation, because of the loss of quiescence, increased apoptosis, and reduced multiple-lineage terminal differentiation potential. Bioinformatic analysis revealed that the hematopoietic stem cells exit of quiescence and commit to differentiation, which lead to hematopoietic stem cells exhaustion. Mechanistically, we attribute an important Setd2 function in murine adult hematopoietic stem cells to the inhibition of the Nsd1/2/3 transcriptional complex, which recruits super elongation complex and controls RNA polymerase II elongation on a subset of target genes including Myc. Our results reveal a critical role of Setd2 in regulating quiescence and differentiation of HSCs through restricting the NSDs/SEC mediated RNA Polymerase II elongation.
2018-05-01 | GSE112550 | GEO
Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. It is now known that primary iPS cells often carry genomic aberrations and these abnormality may compromise their possibility of clinical application. We analysed primary hIPSC lines derived from monoclonal human endothelial progenitor cell lines by array-based comparative genomic hybridisation.
2014-04-04 | E-MTAB-1319 | biostudies-arrayexpress
Project description:Hematopoietic stem cells give rise to all blood lineages, can fully re-populate the bone marrow, and easily outlive the host organism. To better understand how stem cells remain fit during aging, we analyzed the proteome of hematopoietic stem and progenitor cells.
2019-05-23 | MSV000083845 | MassIVE
Project description:This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.
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Project description:The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to bedside translation of novel and more efficient protocols of cell transplantation in central nervous system (CNS) myelin disorders. We have performed the transcriptome analysis in the spinal cord of mice with sham treated Experimental Animal Encephelomyletis (EAE), miPSC-NPC treated EAE mice and naive mice, in order understand the gene expression changes related to the miPSC-NPC treatment.
2016-06-03 | E-MTAB-1546 | biostudies-arrayexpress
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