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Astrocyte-to-astrocyte contact and a positive feedback loop of growth factor signaling regulate astrocyte maturation

ABSTRACT: Astrocyte-to-astrocyte contact and a positive feedback loop of growth factor signaling regulate astrocyte maturation

PROVIDER: PRJNA516915 | ENA |

REPOSITORIES: ENA

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Astrocyte-to-astrocyte contact and a positive feedback loop of growth factor signaling regulate astrocyte maturation.

Project description: Not available

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Astrocyte-to-astrocyte contact and a positive feedback loop of growth factor signaling regulate astrocyte maturation

Project description:Astrocytes were purified from postnatal day 2 mouse cortices by immunopanning with HepaCAM. Inhibitors and DMSO were added on in-vitro day 2. HBEGF was depleted on the cell prep day and till in-vitro day 7. In-vitro day 2, 7 and 14 samples were collected on designed timepointed.

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Analyses of RNAi-heterochromatin positive feedback loop in Tetrahymena

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A positive feedback loop controls Toxoplasma chronic differentiation

Project description:Successful infection strategies must balance pathogen amplification and persistence. In Toxoplasma gondii, this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. We examine five factors transcriptionally activated by BFD1. One of these is a cytosolic RNA-binding protein of the CCCH-type zinc finger family, which we name BFD2. Parasites lacking BFD2 fail to induce BFD1 and are consequently unable to fully differentiate in culture or in mice. BFD2 interacts with the BFD1 transcript under stress and deletion of BFD2 reduces BFD1 protein levels, but not mRNA abundance. The reciprocal effects on BFD2 transcription and BFD1 translation outline a positive feedback loop that enforces commitment to differentiation. BFD2 helps explain how parasites commit to the chronic gene-expression program and elucidates how the balance between proliferation and persistence is achieved over the course of infection.

2023-08-07 | PXD039648 | Pride

A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signaling in Toxoplasma gondii.

Project description:Fundamental processes of obligate intracellular parasites, such as Plasmodium falciparum and Toxoplasma gondii are controlled by a set of plant-like calcium dependent kinases (CDPKs), the conserved cAMP- and cGMP-dependent protein kinases (PKA and PKG), second messengers and lipid signalling. While some major components of the signalling networks have been identified, how these are connected is largely not known. Here, we compare the phospho-signalling networks during Toxoplasma egress from its host cell by artificially raising cGMP or calcium levels to activate PKG or CDPKs, respectively. We show that both these inducers trigger near identical signalling pathways and provide evidence for a feedback loop involving CDPK3. We measure phospho- and lipid signalling in parasites treated with the Ca2+ ionophore A23187 in a sub-minute timecourse and show CDPK3-dependent regulation of diacylglycerol levels and increased phosphorylation of four phosphodiesterases (PDEs), suggesting their function in the feedback loop. Disruption of CDPK3 leads to elevated cAMP levels and inhibition of PKA signalling rescues the egress defect of ΔCDPK3 parasites treated with A23187. Biochemical analysis of the four PDEs identifies PDE2 as the only cAMP-specific PDE among these candidates while the other PDEs are cGMP specific; two of which are inhibited by the predicted PDE inhibitor BIPPO. Conditional deletion of the 4 PDEs supports an important, but non-essential role of PDE1 and PDE2 for growth, while only the latter plays a role in controlling A23187-mediated egress. In summary, we uncover a positive feedback loop that potentiates signalling during egress and links several signalling pathways together.

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A runaway PRH/HHEX-Notch3 feedback loop drives cholangiocarcinoma (ChIP-seq)

Project description:PRH/HHEX-Notch3 feedback loop drives cholangiocarcinoma

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A runaway PRH/HHEX-Notch3 feedback loop drives cholangiocarcinoma (RNA-Seq)

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Project description:ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates in skin fibrosis pathogenesis

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