Ontology highlight
ABSTRACT:
PROVIDER: PRJNA529366 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We aim at understanding how ionizing radiations (IR) increase the risk of developing myeloid leukemia. We recently showed that IR leads to the derepression of retroelements. We demonstrated that retroelements expression in aged HSCs is regulated by the heterochromatin repressive histone mark H3K9me3. However, the mechanisms by which IR specifically triggers retroelements expression in HSCs are unknown. We hypothesized that retroelements derepression is due to IR-induced heterochromatin changes. To answer this question, we performed H3K9me3 ChIP-seq experiments in hematopoietic stem cells sorted from mice one month after they were irradiated and compared them to controls hematopoietic stem cells sorted from non-irradiated mice.
2022-06-24 | E-MTAB-11865 | biostudies-arrayexpress
Project description:We aim at understanding how ionizing radiations (IR) increase the risk of developing myeloid leukemia. We recently showed that IR leads to the derepression of retroelements. Retroelements are major contributors of gene regulatory networks. However, the impact of retroelements derepression on the HSC transcriptome and function remains to be addressed. We hypothesized that retroelements derepression is involved in HSC transcriptomic alterations. To answer this question, we performed RNA-seq experiments in hematopoietic stem cells sorted from mice one month after they were irradiated and compared them to controls hematopoietic stem cells sorted from non-irradiated mice.
2022-06-24 | E-MTAB-11866 | biostudies-arrayexpress
Project description:Infections are associated with extensive consumption of blood platelets representing a high risk for health. How the hematopoietic system coordinates the rapid and efficient regeneration of this particular lineage during such stress scenarios remains unclear. Here we report that the phenotypic hematopoietic stem cell (HSC) compartment contains highly potent megakaryocyte-committed progenitors (hipMkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults. Our data show that during homeostasis, hipMkPs are maintained in a primed but quiescent state, thus contributing little to steady-state megakaryopoiesis. Moreover, homeostatic hipMkPs show expression of megakaryocyte lineage priming transcripts for which protein synthesis is suppressed. We demonstrate that acute inflammatory signaling instructs activation of hipMkPs, as well as Mk protein production from pre-existing transcripts and drives a rapid maturation of hipMkPs and other Mk progenitors. This results in an efficient regeneration of platelets that are lost during inflammatory insult. Thus, our study reveals an elegant emergency machinery that counteracts life-threating depletions in the platelet pool during acute inflammation.
2015-08-26 | PXD001500 | Pride
Project description:The type I interferon (IFN) response is inactive during early mammalian development and becomes functional only after gastrulation. As a result, the totipotent and pluripotent embryonic stages remain susceptible to pathogens, including viruses. Here, we demonstrate that pluripotent mouse embryonic stem cells (mESCs) suppress the RIG-I-like receptor sensing pathway by silencing the expression of the dsRNA sensor MDA5. This silencing is necessary to avoid the recognition of dsRNAs of endogenous origin, which accumulate in mESCs. Reintroducing MDA5 results in recognition of these endogenous dsRNAs and triggers the activation of the IFN response through IRF3. The production of IFN alters the differentiation ability of mESCs, and affects the pluripotency gene expression program, as shown by epigenetic, transcriptomic and proteomic analyses. These findings are conserved in zebrafish, where MDA5 is also expressed at later developmental stages. Similarly, zebrafish lack earlystage IFN activation, and dsRNA-mediated signalling results in developmental defects. Altogether, we conclude that silencing the RIG-I-like receptor pathway during early development is widely conserved and is essential to prevent aberrant immune recognition of endogenous dsRNAs, safeguarding normal development.
2025-09-26 | PXD059977 | Pride
Project description:The type I interferon (IFN) response is inactive during early mammalian development and becomes functional only after gastrulation. As a result, the totipotent and pluripotent embryonic stages remain susceptible to pathogens, including viruses. Here, we demonstrate that pluripotent mouse embryonic stem cells (mESCs) suppress the RIG-I-like receptor sensing pathway by silencing the expression of the dsRNA sensor MDA5. This silencing is necessary to avoid the recognition of dsRNAs of endogenous origin, which accumulate in mESCs. Reintroducing MDA5 results in recognition of these endogenous dsRNAs and triggers the activation of the IFN response through IRF3. The production of IFN alters the differentiation ability of mESCs, and affects the pluripotency gene expression program, as shown by epigenetic, transcriptomic and proteomic analyses. These findings are conserved in zebrafish, where MDA5 is also expressed at later developmental stages. Similarly, zebrafish lack early-stage IFN activation, and dsRNA-mediated signalling results in developmental defects. Altogether, we conclude that silencing the RIG-I-like receptor pathway during early development is widely conserved and is essential to prevent aberrant immune recognition of endogenous dsRNAs, safeguarding normal development.
2025-09-26 | GSE289814 | GEO
Project description:Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral double-stranded RNA (dsRNA) sensor that induces antiviral immune response. We here demonstrate that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNA because its filament formation on dsRNA is impaired by the imperfect duplex structure, AGS-variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNA. Moreover, we identified an unexpected role of RNA-rich cellular environment in suppressing aberrant MDA5 oligomerization, highlighting context-dependence of self vs. non-self discrimination. Overall, our work demonstrates that the increased efficiency of MDA5 to recognize dsRNA comes at a cost of self-recognition, and implicates a unique role of Alu RNAs as virus-like elements that shape the primate immune system.
2018-01-29 | GSE104864 | GEO
Project description:Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral double-stranded RNA (dsRNA) sensor that induces antiviral immune response. We here demonstrate that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNA because its filament formation on dsRNA is impaired by the imperfect duplex structure, AGS-variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNA. Moreover, we identified an unexpected role of RNA-rich cellular environment in suppressing aberrant MDA5 oligomerization, highlighting context-dependence of self vs. non-self discrimination. Overall, our work demonstrates that the increased efficiency of MDA5 to recognize dsRNA comes at a cost of self-recognition, and implicates a unique role of Alu RNAs as virus-like elements that shape the primate immune system.
2018-01-29 | GSE103539 | GEO
Project description:Reverse transcription-derived sequences account for at least half of the human genome. Although these retroelements are formidable motors of evolution, they can occasionally cause disease, and accordingly are inactivated during early embryogenesis through epigenetic mechanisms. In the mouse, at least for endogenous retroviruses, important mediators of this process are the tetrapod-specific KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor TRIM28. The present study demonstrates that KRAB/TRIM28-mediated regulation is responsible for controlling a very broad range of human-specific endogenous retroelements (EREs) in human embryonic stem (ES) cells and that it exerts, as a consequence, a marked effect on the transcriptional dynamics of these cells. It further reveals reciprocal dependence between TRIM28 recruitment at specific families of EREs and DNA methylation. It finally points to the importance of persistent TRIM28-mediated control of ERE transcriptional impact beyond their presumed inactivation by DNA methylation. Analyses of epigentic effectors and marks in KAP1 WT and KD human embryonic stem cells
2014-05-29 | E-GEOD-57989 | biostudies-arrayexpress