This SuperSeries is composed of the SubSeries listed below.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesAutophagy is critical for protecting HSCs from metabolic stress. Here, we used a genetic approach to inactivate autophagy in adult HSCs by deleting the Atg12 gene. We show that loss of autophagy causes accumulation of mitochondria and an oxidative phosphorylation (OXPHOS)-activated metabolic state, which drives accelerated myeloid differentiation likely through epigenetic deregulations rather than transcriptional changes, and impairs HSC self-renewal activity and regenerative potential.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesTesticular and ovarian gene expression changes with loss of DMXL2
Dual role of DMXL2 in olfactory information transmission and the first wave of spermatogenesis.
Specimen part
View SamplesTo identify the molecular characterisitics of parallel lineage-biased MPP populations arising from hematopoietic stem cells (HSC) we conducted genome-wide analyses of hematopoietic stem, progenitor and mature myeloid cell populations using Affymetrix Gene ST1.0 arrays.
Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions.
Specimen part
View SamplesMultipotent stromal cells (MSC) and their osteoblastic lineage cell (OBC) derivatives are part of the bone marrow (BM) niche and contribute to hematopoietic stem cell (HSC) maintenance. During myeloproliferative neoplasm (MPN) development, MSCs are stimulated to overproduce functtionally altered OBCs, which accumulate in the BM cavity as myelofibrotic cells. These MPN-expanded OBCs, in turn, impair the maintenance of normal HSCs but not of leukemic stem cells.
Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche.
Specimen part, Time
View SamplesLoss of Rb family in HSCs results in a severe phenotype, such as enhanced proliferation and increase in stem cell number. In addition, HSCs were higly mobilized but failed to transplant. Rb family deficient mice rapidly exhibit a myeloproliferative disease with eosinophilic characteristics. Meanwhile, the lymphoid compartment was severely decreased, due to high apoptotic activity in this lineage.
Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family.
No sample metadata fields
View SamplesEpigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion between pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem and progenitor cells (HSPCs), and mature hematopoietic cells. Quantification of chromatin composition by high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSPCs, with a further reduction in euchromatin as HSPCs transition into mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9a resulted in delayed hematopoietic stem cell (HSC) differentiation. Our results demonstrate significant global rearrangements of chromatin structure during embryonic and adult stem cell differentiation, and that heterochromatin formation by H3K9 methylation is an important regulator of HSC differentiation. Overall design: Examination of gene expression profile of in vitro cultured mouse HSC with the G9a inhibitor UNC0638
Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells.
Specimen part, Cell line, Treatment, Subject
View SamplesThis study investigated possible molecular changes in the oral mucosa of head and neck squamous cell carcinoma patients submitted to chemoradiotherapy with and without low-level laser therapy by cDNA microarray analysis.
cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study.
Specimen part, Disease, Disease stage
View SamplesSingle cell RNA Seq and bioinformatic analysis are used to study what processes are important for the molecular reprogramming of GMPs after 5-FU treatment. Samples were collected at different time points (0, 8, 10, 12 and 14 days post treatment) Overall design: Single cell RNA sequencing of GMP cells upon 5-FU treatment
Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis.
Specimen part, Cell line, Treatment, Subject, Time
View SamplesWe examined the biological effects of a potent second-generation proteasome inhibitor, ixazomib, in T-cell lymphoma and Hodgkin lymphoma cell lines and human xenograft models. Ixazomib resulted in time- and dose-dependent cytotoxicity and apoptosis in all cell lines (IC50s <75nM). In vivo studies via SCID tumor xenografts showed significant inhibition of tumor growth (P<0.001) with significantly improved survival (P<0.001) in Jurkat and L540 models with ixazomib-treated mice versus controls. Through global transcriptome and network analyses, ixazomib-treated Jurkat and L540 cells showed significant overlap in biological functions involved in regulation of cell cycle, chromatin modification, and DNA repair processes with a lack of conservation observed in a relatively ixazomib-resistant cell line, L428. Moreover, the predicted activation and inhibition status of tumor suppressors and oncogenes strongly favored ixazomib inhibition of tumor progression. Most notably, ixazomib down-regulated protein levels of MYC and its target genes. Additionally, chromatin immunoprecipitation showed that histone H3 acetylation affected MYC levels and cell death response to ixazomib. Furthermore, inhibition of MYC with JQ1 resulted in synergistic cell death in L428, which was confirmed utilizing MYC knockout. Collectively, ixazomib down-regulated MYC and downstream substrates in TCL and HL, while resistance appeared mediated through MYC- and CHK1-dependent mechanisms.
Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma.
Specimen part, Treatment
View Samples