RNA-seq of DRG neurons isolated from alum vs. alum+KLH immunized mice
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ABSTRACT:
PROVIDER: PRJNA427271 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: we have performed RNA-seq analysis of sensory neurons isolated from alum vs. alum+KLH immunized mice
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Project description:The Canarypox/gp120/Alum vaccines decreased the risk of HIV acquisition in humans. We demonstrate here the efficacy of this vaccine regimen also in the SIVmac251 macaque model when we used the alum but not the MF59 adjuvant. Analysis of innate and adaptive cell responses, envelope antibodies Fc profiles and glycoforms demonstrated a lower inflammatory response with alum than MF59. Alum elicited mucosal V2 peptide-specific IgG associated with vaccine efficacy whereas the MF59 induced mucosal V2 peptide-specific IgG associated with increased risk of infection. Alum modulated the expression of 12 genes, 7 of which are part of the RAS pathway, that correlates with vaccine efficacy and were linked to innate responses that preserve mucosal integrity and adaptive mucosal antibody response to V2. Thus, activation of the RAS pathway, preservation of mucosal integrity and mucosal antibody to V2 in concert, reduce the risk of SIVmac251 acquisition.
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Project description:Although DNA methylation plays a critical role in the development and function of mammalian central nervous system (CNS), its role in peripheral neurons has not been elucidated. To address this issue, we produced conditional knockout mice (CKO) specifically deleting the gene for maintenance DNA methyltransferase 1 (Dnmt1) during the development of neural crest cells. Despite global hypomethylation in the embryonic dorsal root ganglion (DRG) of the CKO mice, the number of sensory neurons was relatively unaffected. However, expression of many genes required for sensory neuron development was altered in embryonic mutant DRG, including down-regulation of Runx1 and TrkA genes as well as up-regulation of Id1 and Dtx1, two negative regulators for neurogenesis. Accompanied with the downregulation of an NGF receptor TrkA, the peripheral axonal projection and the branching of sensory neurons were impaired. Furthermore, the expression of the neuropeptide Galanin and several vanilloid receptors such as TrpV1 and TrpM8 were not detected in the DRG of the CKO mice during late embryonic and neonatal stages, suggesting that DNA methylation regulates the differentiation program for a subset of nociceptive sensory neurons. Taken together, our findings suggest that through transcriptional regulation of key developmental genes in sensory neurons, DNA methylation play a key role in the control of the axonal projection and fate specification of peripheral sensory neurons.
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