Search results for "hematopoietic stem cells"
showing 10 items of 97 documents
Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow
2014
How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-l-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell…
Candida albicans triggers proliferation and differentiation of hematopoietic stem and progenitor cells by a MyD88-dependent signaling.
2009
As TLRs are expressed by hematopoietic stem and progenitor cells, these receptors may play a role in hematopoiesis in response to pathogens during infection. We showed here that inactivated yeasts and hyphae of Candida albicans induce in vitro the proliferation of purified murine hematopoietic stem and progenitor cells (Lin(-)c-Kit(+) Sca-1(+)) as well as their differentiation to lineage positive cells, through a MyD88-dependent pathway. These results indicate that TLR-mediated recognition of C. albicans by hematopoietic stem and progenitor cells may augment the host capability for rapidly replenishing the innate immune system during candidiasis.
Extramedullary Expansion of Hematopoietic Progenitor Cells in Interleukin (IL)-6–sIL-6R Double Transgenic Mice
1997
Soluble cytokine receptors modulate the activity of their cognate ligands. Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can activate cells expressing the gp130 signal transducer lacking the specific IL-6R. To investigate the function of the IL-6–sIL-6R complex in vivo and to discriminate the function of the IL-6–sIL-6R complex from the function of IL-6 alone, we have established a transgenic mouse model. Double-transgenic mice coexpressing IL-6 and sIL-6R were generated and compared with IL-6 and sIL-6R single-transgenic mice. The main phenotype found in IL-6–sIL-6R mice was a dramatic increase of extramedullary hematopoietic progenitor cells in liver and spleen…
Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System
2015
SummaryDuring early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism’s lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed …
Stress response in mesoangioblast stem cells
2006
Stem cells are presumed to survive various stresses, since they are recruited to areas of tissue damage and regeneration, where inflammatory cytokines and cytotoxic cells may result in severe cell injury. We explored the ability of mesoangioblasts to respond to different cell stresses such as heat, heavy metals and osmotic stress, by analyzing heat shock protein (HSP)70 synthesis as a stress indicator. We found that the A6 mesoangioblast stem cells constitutively synthesize HSP70 in a heat shock transcription factor (HSF)-independent way. However, A6 respond to heat shock and cadmium treatment by synthesizing HSP70 over the constitutive expression and this synthesis is HSF1 dependent. The e…
Generation of tumor-reactive CTL against the tumor-associated antigen HER2 using retrovirally transduced dendritic cells derived from CD34+ hemopoiet…
2000
Abstract Ag-specific CD8+ CTL are crucial for effective tumor rejection. Attempts to treat human malignancies by adoptive transfer of tumor-reactive CTL have been limited due to the difficulty of generating and expanding autologous CTL with defined Ag specificity. The current study examined whether human CTL can be generated against the tumor-associated Ag HER2 using autologous dendritic cells (DC) that had been genetically engineered to express HER2. DC progenitors were expanded by culturing CD34+ hemopoietic progenitor cells in the presence of the designer cytokine HyperIL-6. Proliferating precursor cells were infected by a retroviral vector encoding the HER2 Ag and further differentiated…
Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs
2015
International audience; Fanconi anemia is a DNA repair-deficiency syndrome mainly characterized by cancer predisposition and bone marrow failure. Trying to restore the hematopoietic function in these patients, lentiviral vector-mediated gene therapy trials have recently been proposed. However, because no insertional oncogenesis studies have been conducted so far in DNA repair-deficiency syndromes such as Fanconi anemia, we have carried out a genome-wide screening of lentiviral insertion sites after the gene correction of Fanca-/- hematopoietic stem cells (HSCs), using LAM-PCR and 454-pyrosequencing. Our studies first demonstrated that transduction of Fanca-/- HSCs with a lentiviral vector d…
Frequency of CD8+ T Lymphocytes Specific for Lytic and Latent Antigens of Epstein–Barr Virus in Healthy Virus Carriers
1999
Abstract We investigated CD8 + T cell frequencies of five different Epstein–Barr virus-specific cytotoxic T lymphocyte epitopes located within proteins of the replicative cycle and the latent state in healthy long-term virus carriers with IFN-γ enzyme-linked immunospot assay. Frequencies of the HLA-A3-restricted epitope RVRAYTYSK (RVR) whose minimal length was mapped in this study to amino acid position 148–156 of the immediate-early protein BRLF1 were compared with those of a further known HLA-A3-restricted epitope within EBNA3A, RLRAEAQVK (RLR). Determination of frequencies of CD8 + T lymphocytes directed against lytic antigen epitope RVR revealed that only one of eight donors recognized …
AN IL-6/IL-6 SOLUBLE RECEPTOR (IL-6R) HYBRID PROTEIN (H-IL-6) INDUCES EPO-INDEPENDENT ERYTHROID DIFFERENTIATION IN HUMAN CD34+CELLS
2000
H-IL-6 is a hybrid protein constructed to contain IL-6 and its soluble receptor linked by a flexible peptide chain. Here we show that H-IL-6 strongly enhances proliferation of human CD34(+)cells in serum-free liquid culture, and that the majority of the cells generated belong to the erythroid lineage, being positive for the marker Glycophorin A. Conversely, H-IL-6 does not increase the number of myeloid, CD13-positive cells. Comparable effects are observed on progenitors from cord blood and adult peripheral blood. Therefore, H-IL-6 triggers an erythroid-inducing signal in haematopoietic progenitor cells, independently from erythropoietin (EPO).
TTAS a New Stilbene Derivative that Induces Apoptosis in Leishmania Infantum
2012
Leishmania parasites are able to undergo apoptosis (programmed cell death), similarly to mammalian cells. Recently it was demonstrated in vitro the anti-leishmanial effect of some natural and synthetic stilbenoids including resveratrol and piceatannol. In this study we evaluated the Leishmanicidal activity of a pool of stilbene derivatives which had previously shown high apoptotic efficacy against neoplastic cells. All the compounds tested were capable to decrease the parasite viability in a dose-dependent manner. Trans-stilbenes proved to be markedly more effective than cis-isomers. This was different from that observed in tumor cells in which cis-stilbenes were more potent cytotoxic agent…