Similar Datasets
Project description:Here we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is unique to aging. We used single cell RNA sequencing (scRNA-seq) to analyze age specific platelet pathway at the clonal level.
2024-05-21 | GSE255019 | GEO
Project description:Ex vivo production of induced megakaryocytes (MKs) and platelets from stem cells is an alternative approach for supplying transfusible platelets. However, it is still difficult to generate large numbers of MKs and platelets from cord blood hematopoietic stem cells. To optimize the differentiation efficiency of megakaryocytic cells from hematopoietic stem and progenitor cells (HSPCs), we first employed a platelet factor 4 (PF4)-promoter reporter and high-throughput screening strategy to screen for small molecules. We found that a small molecule, Ricolinostat, efficiently promoted the generation of CD34+CD41+ megakaryocyte progenitor cells (MkPs) and CD41+CD61+ MKs from cord blood HSPCs. Ricolinostat showed the capacity to enhance the cell fate commitment of MkPs from HSPCs and promoted the proliferation of CD34+CD41+ MkPs. Ricolinostat significantly increased the gene expression levels of key MK transcriptional factors, including HOXC6 and PCGF2. Notably, these megakaryocytic cells generated from Ricolinostat-induced HSPCs could differentiate into mature MKs and platelets. Additionally, RNA sequencing data suggested that Ricolinostat might enhance MkP fate mainly by inhibiting the secretion of IL-8 and decreasing the expression of IL-8 receptor CXCR2. Our study will help in the development of manufacturing protocols for large-scale generation of induced MKs and platelets for clinical application.
2022-02-09 | GSE182181 | GEO
Project description:Advanced age drives the progressive degeneration of mammalian hair follicles (HF) and termination of its regeneration cycle. The role of hair follicle dermal stem cell (hfDSC) in this age-associated HF dysfunction remains largely unexplored. Here, we first characterize a novel function of hfDSCs in regenerating the full dermal papilla (DP) after laser ablation. Next, we performed long-term fate mapping, age-dependant in vivo clonal analysis and in vitro proliferation assay on hfDSCs to describe the age-related defects in mesenchymal stem cell self-renewal and differentiation capabilities. Moreover, single-cell RNA-sequencing of the HF mesenchymal population mapped the intrinsic transcriptional changes that may drive their age-related dysfunction. We highlight the requirement of hfDSCs for normal HF regeneration. Our findings characterize a novel function of mesenchymal stem cells, and how this crucial cell becomes dysfunctional with age to drive age-related hair loss.
2020-04-20 | GSE115424 | GEO
Project description:In this series we have analyzed the effect of donor age on the gene expression profile of human hematopoietic stem and progenitor cells (HPC). Cells were taken from umbilical cord blood (CB) or from G-CSF mobilized blood of healthy donors for allogeneic blood stem cell transplantation.
2009-06-12 | GSE12277 | GEO
Project description:Megakaryopoiesis is a complex process that involves major cellular changes and relies on controlled coordination of cellular proliferation and differentiation. These mechanisms are orchestrated in part by transcriptional regulators. The key hematopoietic transcription factor SCL/TAL1 is required for specification of the megakaryocytic lineage from hematopoietic progenitors. Here, we report that it also critically controls terminal megakaryocyte maturation. In vivo depletion of SCL specifically in the megakaryocytic lineage affects all key attributes of megakaryocyte progenitors (MkPs), namely proliferation, ploidisation, cytoplasmic maturation, as well as platelet production. Genome-wide expression analysis reveals increased expression of the cell cycle regulator p21 in Scl-deleted MkPs. Importantly, P21 knockdown-mediated rescue assays in Scl-deleted MkPs show full restoration of cell cycle progression and partial rescue of the nuclear and cytoplasmic maturation defects. Therefore, SCL-mediated transcriptional control of p21 is critical for maturation of MkPs. Our study provides a mechanistic link between one of the major hematopoietic transcriptional regulators, cell cycle progression and megakaryocytic differentiation.
2011-07-11 | GSE24969 | GEO
Project description:Purpose: Characterize functional alterations in stem cells and paneth cells obtained from young and aged mice, focusing on age-based impairment of intestinal regeneration due to a decline in canonical Wnt signaling. Methods: mRNA profiles of young and aged stem and paneth cells were generated in triplicate (with one additional young paneth sample) using the Illumina HiSeq 2500. Reads that passed quality filters were aligned to the mm10 mouse genome with annotations provided by UCSC. Results: Approximately 10 millions reads were aligned per sample, corresponding to 36186 transcripts -- of these, 19574 exhibited reasonable expression. The effect of age was tested wtihin paneth and stem cells, using unpaired t-tests with a p-value cutoff of 0.05 and fold change cutoff of 1.5. Within paneth cells, 1025 genes were significant; within stem cells, 750 genes exhibited differential regulation. Among the downregulated genes in paneth and stem cells, we observed significant enrichment of canonical Wnt signaling genes. Conclusion: Age-related downregulation of canonical Wnt signaling is involved in the impairment of intestinal regulation upon aging.
2017-03-14 | GSE84061 | GEO
Project description:Thrombosis is a common complication of end-stage renal disease, particularly in patients on hemodialysis. Although substantial progress has been made in preventing thrombotic complications in various other groups of patients, the mechanisms of thrombosis during hemodialysis require clarification. In this report, we demonstrate that complement activation triggered by hemodialysis biomaterials, and the subsequent generation of the complement anaphylatoxin C5a, results in the expression of functionally active tissue factor (TF) in peripheral blood neutrophils. Because TF is a key initiator of coagulation in vivo, we postulate that the recurring complement activation that occurs during long-term hemodialysis contributes to thrombosis in dialyzed end-stage renal disease patients. Furthermore, we found that complement contributed to the induction of granulocyte colony-stimulating factor, which has been implicated in the pathogenesis of thrombosis in patients treated with the recombinant form of this molecule. Importantly, the inhibition of complement activation attenuated the TF expression and granulocyte colony-stimulating factor induction in blood passing through a hemodialysis circuit, suggesting that the complement system could become a new therapeutic target for preventing thrombosis in patients with chronic renal failure who are maintained on hemodialysis.
| S-EPMC3086498 | biostudies-literature
Project description:Bacillus altitudinis strain:AGE-B8 | isolate:AGE-B8 Genome sequencing and assembly
| PRJNA675729 | ENA
Project description:BackgroundThe objective of this study was to determine if mechanistic target of rapamycin (mTOR) inhibition with or without AMP-activated protein kinase (AMPK) activation can protect against primary, age-related OA.DesignDunkin-Hartley guinea pigs develop mild primary OA pathology by 5 months of age that progresses to moderate OA by 8 months of age. At 5 months, guinea pigs served as young control (n = 3) or were fed either a control diet (n = 8), a diet enriched with the mTOR-inhibitor rapamycin (Rap, 14 ppm, n = 8), or Rap with the AMPK-activator metformin (Rap+Met, 1000 ppm, n = 8) for 12 weeks. Knee joints were evaluated by OARSI scoring, micro-computed tomography, and immunohistochemistry. Glenohumeral articular cartilage was collected for western blotting.ResultsRap- and Rap+Met-treated guinea pigs displayed lower body weight than control. Rap and Rap+Met inhibited articular cartilage mTORC1 but not mTORC2 signaling. Rap+Met, but not Rap alone, stimulated AMPK. Despite lower body weight and articular cartilage mTORC1 inhibition, Rap- and Rap+Met-treated guinea pigs had greater OA severity in the medial tibial plateau due to articular cartilage structural damage and/or proteoglycan loss. Rap and Rap+Met increased plasma glucose compared to control. Plasma glucose concentration was positively correlated with proteoglycan loss, suggesting hyperglycemic stress after Rap treatment was related to worsened OA.ConclusionsThis is the first study to show that Rap induced increase in plasma glucose was associated with greater OA severity. Further, articular cartilage mTORC1 inhibition and bodyweight reduction by dietary Rap and Rap+Met did not appear to protect against primary OA during the prevailing hyperglycemia.
| S-EPMC8495984 | biostudies-literature
Project description:Megakaryopoiesis is a complex process that involves major cellular changes and relies on controlled coordination of cellular proliferation and differentiation. These mechanisms are orchestrated in part by transcriptional regulators. The key hematopoietic transcription factor SCL/TAL1 is required for specification of the megakaryocytic lineage from hematopoietic progenitors. Here, we report that it also critically controls terminal megakaryocyte maturation. In vivo depletion of SCL specifically in the megakaryocytic lineage affects all key attributes of megakaryocyte progenitors (MkPs), namely proliferation, ploidisation, cytoplasmic maturation, as well as platelet production. Genome-wide expression analysis reveals increased expression of the cell cycle regulator p21 in Scl-deleted MkPs. Importantly, P21 knockdown-mediated rescue assays in Scl-deleted MkPs show full restoration of cell cycle progression and partial rescue of the nuclear and cytoplasmic maturation defects. Therefore, SCL-mediated transcriptional control of p21 is critical for maturation of MkPs. Our study provides a mechanistic link between one of the major hematopoietic transcriptional regulators, cell cycle progression and megakaryocytic differentiation. Total RNA extracted from control TGPF4-CRE;SCL wt/wt sorted MK progenitors was compared to total RNA extracted from TGPF4-CRE;SCL fl/fl MK progenitors cells where Scl was completely excised
2011-07-11 | E-GEOD-24969 | biostudies-arrayexpress