The hematopoietic stem cell (HSC) compartment consists of a small pool of cells capable of replenishing all blood cells. Although it is established that the hematopoietic system is assembled as a hierarchical organization under steady-state conditions, emerging evidence suggests that distinct differentiation pathways may exist in response to acute stress. However, it remains unclear how different hematopoietic stem and progenitor cell subpopulations behave under sustained chronic stress. Here, by using adult transgenic mice over-expressing erythropoietin (EPO; Tg6) and a combination of in vivo, in vitro, and deep sequencing approaches, we found that HSCs respond differentially to chronic erythroid stress than their closely related multipotent progenitors (MPPs). Specifically, HSCs exhibit a vastly committed erythroid progenitor profile with enhanced cell division, while MPPs display erythroid and myeloid cell signatures and an accumulation of uncommitted cells. Thus, our results identify HSCs as master regulators of chronic stress erythropoiesis, potentially circumventing the hierarchical differentiation-detour. Overall design: HSC and MPP from WT or Tg mice were analyzed in triplicates.
Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice.
Specimen part, Cell line, Subject
View SamplesPHD4 regulates the expression of Hypxia-inducible Factor 2 (HIF-2) alpha in LM8 osteosarcoma cells. PHD4 overexpression inhibits the growth of experimental tumor in syngenic mice but stimulates angiogenesis via Transforming Growth-Factor (TGF)-alpha.
PHD4 stimulates tumor angiogenesis in osteosarcoma cells via TGF-α.
Cell line, Treatment
View SamplesObjective: Transcriptional profiling of murine HSPC in response to ß-glucan-induced innate immune training Overall design: HSPC mRNA profiles of wild type (WT) mice injected with PBS or ß-glucan. Wild type (WT) C57BL/6 mice were intraperitoneally injected with PBS or 1 mg ß-glucan in PBS. Mice were sacrificed on day 7 or day 28 and long-term heematopoietic stem cells (LT-HSC) and/or multipotent progenitors (MPP) were sorted. In another group, mice were injected with PBS or 1 mg ß-glucan in PBS and on day 7 they were additionally injected with 150 mg/kg 5-fluouracil. Mice were sacrificed on day 14 after 5-FU administration and LT-HSC were sorted.
Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.
Age, Specimen part, Cell line, Subject
View SamplesIn most embryos, the mid-blastula transition is a complex process featuring maternal RNA degradation, cell cycle pause, zygotic transcriptional activation and morphological changes. The nucleocytoplasmic (N/C) ratio has been proposed to control the multiple events at MBT. To understand the global transcriptional response to the changes of the N/C ratio, we profiled wild type and haploid embryos using cDNA microarrays at three developmental stages.
Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition.
No sample metadata fields
View SamplesKaposis sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response.
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 3 inhibits gamma interferon and major histocompatibility complex class II expression.
Specimen part, Cell line
View SamplesThe Early Growth Response (Egr) family of transcription factors consists of 4 members (Egr1-4) that are expressed in a wide variety of cell types. A large body of evidence point to a role for Egr transcription factors in growth, survival, and differentiation. A major unanswered question is whether Egr transcription factors serve similar functions in diverse cell types by activating a common set of target genes. Signal transduction cascades in neurons and lymphocytes show striking parallels. Activation of either cell type activates the Ras-MAPK pathway and, in parallel, leads to increases in intracellular calcium stimulating the calcineurin-NFAT pathway. In both cell types, the strength of the activation signal affects the cellular outcomes and very strong stimuli lead to cell death. Notably both these pathways converge on the induction of Egr genes. We believe that downstream targets of Egr transcription factors in lymphocytes may also be activated by Egr factors in activated neurons. There is precedence for common target gene activation in these two cell types: apoptosis in both activated T cells and methamphetamine stimulated neurons occurs via FasL induction by NFAT transcription factors. We propose to use developing T lymphocytes (thymocytes) as a model system for discovery of Egr-dependent target genes for several reasons. First, we have observed a prominent survival defect in thymocytes from mice deficient in both Egr1 and Egr3 (1/3 DKO) and a partial differention block in the immature double negative (DN) stage. In addition, thymocytes are an easily manipulatable cell type, and the DN subpopulation affected in 1/3 DKO mice can be isolated to very high purity. We anticipate that 1/3 DKO thymocytes will provide an excellent experimental system that will provide insight into Egr-dependent transcription in neuronal development, activation, and death.
Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesThe goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesDuring acute viral infections, effector CD8+ T cells differentiate into memory precursors or short-lived terminal effectors. miR-17-92a over-expression skews CD8+ effector cells to the terminal differentiation.
Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation.
Specimen part
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