Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and knock-in TrkAC lumbar dorsal roots ganglia transcriptomes in a context of arthritis induced by intra-articular injection of complete Freund's adjuvant
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE164198 | GEO | 2023/01/05
REPOSITORIES: GEO
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Project description:We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its receptor TrkA in neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), which, through the receptor p75, can kill neighboring neurons with low retrograde NGF–TrkA signaling whereas neurons with high NGF–TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. Keywords: comparative gene expression analysis
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Project description:Nerve growth factor (NGF) pays a role in neuronal differentiation and may also play a role in hematopoietic differentiation as shown by synergistic action for the colony formation of CD34 positive hematopoietic progenitor cells treated with M-CSF or SCF. However, the exact role of NGF in hematopoietic system is unclear. It is also not clear whether NGF mediated signals in hematopoietic cells are identical to those in neuronal cells. To study the signal transduction pathways induced by NGF treatment in hematopoietic cells, we utilized the mastocytoma cell line HMC-1 (V560G c-Kit) which expresses the NGF receptor, TrkA, as well as the constitutively activated SCF receptor, V560G c-Kit, which can be inhibited by treatment with tyrosine kinase inhibitor imatinib mesylate. NGF rescues HMC-1 (V560G c-Kit) from imatinib induced cell death and promotes proliferation. To examine the NGF mediated proliferation and survival in these cells, we compared the NGF mediated upregulated genes (30 and 120 min after stimulation) to the downregulated genes by imatinib treatment (downregulation of c-Kit activity for 4 h) by transcriptome analysis. The following conclusions can be drawn from the microarray data: Firstly, gene expression profiling reaveals 50% overlap of genes induced by NGF-TrkA with genes expressed downstream of V560G c-Kit. Secondly, NGF treatment does not enhance expression of genes involved in immune related functions that were down modulated by imatinib. Thirdly, more than 55% of common upregulated genes are involved in cell proliferation and survival. Forthly, we found KLF2 and SMAD7 as the NGF mediated novel down stream genes in hematopoietic cells that may play a role in NGF mediated survival signal in HMC-1 (V560G c-Kit) cells. Keywords: Transcriptome analysis - comparison of TrkA and V560G c-Kit downstream genes in HMC-1 (V560G c-Kit) cells
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