E-GEOD-45194
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA193193
PROVIDER: E-GEOD-45194 | ExpressionAtlas | 2015-07-11
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Oncogenic Nras has a bimodal effect on hematopoietic stem cells promoting proliferation and self-renewal
| PRJNA193193 | ENA
Project description:Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others. 12 RNA samples from mouse bone marrows were analyzed. There are three biological replicates for each subtype.
2014-03-14 | E-GEOD-45194 | biostudies-arrayexpress
Project description:Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others.
2014-03-14 | GSE45194 | GEO
Project description:Ionizing radiation (IR) has long been associated with reduced hematopoietic function and increased malignancies, although the mechanisms behind this relationship remain poorly understood. The carcinogenic effect of IR has been commonly attributed to the direct induction of DNA damage. We demonstrate that IR exposure results in long-term, somatically heritable, cell-intrinsic reductions in HSC self-renewal that is mediated by C/EBP? and reversed by Notch, both of which are associated with human leukemias. Remarkably, restoration of HSC self-renewal prevents selection for C/EBP? loss of function in previously irradiated HSC pools. We propose that environmental insults prompt HSC to initiate a program limiting their self-renewal to prevent damaged HSC from contributing to hematopoiesis. This "programmed mediocrity" is advantageous for the localized insults animals have evolved to deal with, but becomes tumor promoting when the entire HSC compartment is damaged, such as during total body irradiation, by increasing selective pressure for adaptive oncogenic mutations Examination of mRNA levels in in vitro and in vivo Hematopoietic Stem Cell that exposed to IR Ionizing radiation (IR) or control. Each group has three replicates.
2015-07-22 | E-GEOD-61602 | biostudies-arrayexpress
Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis. three NrasG12D/G12D HSCs samples, three NrasG12D/+ HSCs samples, two Nras+/+ HSCs control samples.
2013-05-29 | E-GEOD-46948 | biostudies-arrayexpress
Project description:Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials
| PRJNA531434 | ENA
Project description:G0 marker-separation of dormant and active hematopoietic stem cells reveals dormancy regulation by basal cytoplasmic calcium
2019-12-19 | PXD012093 | JPOST Repository
Project description:Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification and degradation – broadly termed protein homeostasis or “proteostasis” – in these cells is still in its infancy. Here we report the requirement of the small phospho-binding adaptor proteins, the cyclin dependent kinase subunits (Cks1 and Cks2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. Cks1 and Cks2 are critical regulators of a myriad of key intracellular signalling pathways that govern hematopoietic stem cell biology and together they balance protein homeostasis and restrain reactive oxygen species to ensure healthy hematopoietic stem cell function.
2023-03-11 | PXD035984 | Pride
Project description:Increased hematopoietic stem cell (HSC) proliferation in response to infections might reflect enhanced HSC contributions for rapid replenishment of blood and immune cell compartments. However, there is no direct evidence in vivo for enhanced HSC differentiation to natural challenges. Here we studied by non-invasive fate mapping HSC differentiation for a comprehensive set of hematopoietic challenges, including irradiation, polymicrobial sepsis, bleeding, antibody-mediated ablation of granulocytes or B lymphocytes (akin to Rituximab in humans), and genetic lymphocyte deficiency. HSC sensed systemic infection, upregulated transcription factors promoting stem cell self-renewal (Foxp1, Atf4), stem cell maintenance (cMyc and nMyc), transcription in stressed cells (Hsf1) and suppression of apoptosis (E2f4), and enhanced their proliferation. However, none of these acute or chronic hematopoietic stressors enhanced HSC output in situ, suggesting HSC protection and maintenance rather than heightened differentiation. This disconnect may prioritize the long-term integrity of HSC over short-term enhanced productivity in response to hematopoietic perturbations.
2022-12-05 | GSE193322 | GEO
Project description:In the hematopoietic microenvironment, endothelial cells (ECs) play an important role in the regulation of hematopoietic cell proliferation and trafficking. We previously demonstrated that EC stimulated with tumor necrosis factor alpha (TNF-α) induce the generation of dendritic cells from CD34(+) stem cells, whereas in contrast, interleukins were capable of inducing the proliferation of hematopoietic and myeloid progenitors. In order to identify potentially new soluble factors which greatly impact the self-renewal, proliferation and differentiation of CD34+ hematopoietic stem cells (HSC), we examined the expression profiles of IL-1ß, IL-3 and IL-6 stimulated human umbilical vein endothelial cells (HUVEC). we processed seven different umbilical cords and isolated 129 samples for total RNA, and pooled them into 18 groups corresponding to each stimulant, control and time point.
2011-07-01 | E-GEOD-22325 | biostudies-arrayexpress