Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237529 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Granulocyte colony-stimulating factor (G-CSF) has been utilized to treat neutropenia in various clinical settings. Although clearly beneficial, there are concerns that use of G-CSF in certain conditions increases the risk of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The most striking example is in severe congenital neutropenia (SCN). SCN patients develop MDS/AML at a high rate that is directly correlated to the cumulative lifetime dosage of G-CSF. MDS and AML that arise in these settings are commonly associated with chromosomal deletions. We demonstrate that chronic G-CSF treatment in mice results in expansion of the hematopoietic stem cell population. Furthermore, primitive hematopoietic progenitors from G-CSF–treated mice show evidence of DNA damage as demonstrated by an increase in double strand breaks and recurrent chromosomal deletions. Concurrent treatment with genistein, a natural soy isoflavone, limits DNA damage in this population. The protective effect of genistein appears to be related to its preferential inhibition of G-CSF–induced proliferation of hematopoietic stem cells. Importantly, genistein does not impair G-CSF–induced proliferation of committed hematopoietic progenitors, nor diminish neutrophil production. The protective effect of genistein was accomplished with plasma levels that are easily attainable through dietary supplementation. aCGH was performed using NimbleGen
2014-02-07 | GSE54737 | GEO
Project description:Granulocyte colony-stimulating factor (G-CSF) has been utilized to treat neutropenia in various clinical settings. Although clearly beneficial, there are concerns that use of G-CSF in certain conditions increases the risk of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The most striking example is in severe congenital neutropenia (SCN). SCN patients develop MDS/AML at a high rate that is directly correlated to the cumulative lifetime dosage of G-CSF. MDS and AML that arise in these settings are commonly associated with chromosomal deletions. We demonstrate that chronic G-CSF treatment in mice results in expansion of the hematopoietic stem cell population. Furthermore, primitive hematopoietic progenitors from G-CSFM-bM-^@M-^Streated mice show evidence of DNA damage as demonstrated by an increase in double strand breaks and recurrent chromosomal deletions. Concurrent treatment with genistein, a natural soy isoflavone, limits DNA damage in this population. The protective effect of genistein appears to be related to its preferential inhibition of G-CSFM-bM-^@M-^Sinduced proliferation of hematopoietic stem cells. Importantly, genistein does not impair G-CSFM-bM-^@M-^Sinduced proliferation of committed hematopoietic progenitors, nor diminish neutrophil production. The protective effect of genistein was accomplished with plasma levels that are easily attainable through dietary supplementation. aCGH was performed using NimbleGen DNA was extracted from bone marrow samples from mice treated with G-CSF or diluent for 4 months and analyzed using NimbleGen 3x720K mouse copy number arrays
2014-02-07 | E-GEOD-54737 | biostudies-arrayexpress
Project description:iTRAQ-based quantitative proteomics and phosphoproteomics analyses of induced pluripotent stem cells (iPSC) from patients with longstanding type 1 diabetes. "Preserved DNA Damage Checkpoint Pathway Protects From Complications in Long-standing Type 1 Diabetes", Cell Metabolism, in press.
2015-07-08 | MSV000079185 | MassIVE
Project description:Our research has demonstrated that G-CSF impedes engraftment of CRISPR-Cas9 gene edited human hematopoietic stem cells (HSCs) by exacerbating p53-mediated DNA damage response. Results in this study suggest that the potential for G-CSF to exacerbate HSC toxicity mediated by DNA-damaging nucleases should be considered in autologous HSC gene therapy clinical trials.
2023-06-30 | GSE230182 | GEO
Project description:Overexpression of p21 in NEMOΔhepa animals protects against DNA damage, acceleration of hepatocarcinogenesis and cholestasis. As strengthened by our LPS stimulation experiments, we identified a novel protective role of p21 against DNA damage.
2015-03-01 | GSE61100 | GEO
Project description:Overexpression of p21 in NEMOM-NM-^Thepa animals protects against DNA damage, acceleration of hepatocarcinogenesis and cholestasis. As strengthened by our LPS stimulation experiments, we identified a novel protective role of p21 against DNA damage. Expression profiling of livers from wild type, NEMO, and NEMO-P21 null mice.
2015-03-01 | E-GEOD-61100 | biostudies-arrayexpress
Project description:Hematopoietic stem cell quiescence attenuates DNA damage repair and response contributing to age-dependent DNA damage accumulation
| PRJNA239886 | ENA
Project description:Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anti-cancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anti-cancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in a TNBC cell line, MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. In the meantime, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, for the first time, our study present the evidence that genistein could inhibit TNBC cell growth by regulating the cell cycle and DNA damage response. Our findings help elucidate the mechanisms through which genistein exerts its anti-cancer effects in TNBC cells.
2016-01-26 | PXD002735 | Pride
Project description:More mechanistic studies are needed to reveal the hidden details of in vivo-induced trained immunity. Here, using a Candida albicans live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vaccination reprograms hematopoietic stem and progenitor cells (HSPCs) early during infection and mobilize them transiently to the spleen to produce trained macrophages. Trained HSPCs are not only primed for myeloid cell production but also reprogramed to produce a greater amount of proinflammatory cytokines in response to a second challenge; additionally, their adoptive transfer is sufficient to protect mice against reinfection. Mechanistically, autocrine GM-CSF activation of HSPCs is responsible for the trained phenotype and essential for the vaccine-induced protection. Our findings reveal a fundamental role for HSPCs in the trained immune protective response, opening new avenues for disease prevention and treatment.
2021-12-06 | GSE184104 | GEO
Project description:Hematopoietic stem cell (HSC) aging underlies many age-related hematopoietic disorders. Accumulation of DNA damage is a hallmark of HSC aging. Wild-type p53-induced phosphatase 1 (Wip1) is a homeostatic regulator of DNA damage response. We used microarrays to detail the global programme of gene expression in Wip1 KO HSC Wild-type p53-induced phosphatase 1 (Wip1) knockout HSC and Wild type HSC were selected for RNA extraction and hybridization on Affymetrix microarrays.
2014-06-25 | E-GEOD-58754 | biostudies-arrayexpress