Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression profiling of mouse bone marrow pre-B cells

ABSTRACT: Triplicate RNA-seq expression analysis of bone marrow pre-B cells isolated from mice, to demonstrate repertoire at the IgH locus Triplicate RNA-seq expression analysis of bone marrow pre-B cells

ORGANISM(S): Mus musculus

SUBMITTER: Gordon Smyth

PROVIDER: E-GEOD-52868 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia.

Liu Grace J GJ Cimmino Luisa L Jude Julian G JG Hu Yifang Y Witkowski Matthew T MT McKenzie Mark D MD Kartal-Kaess Mutlu M Best Sarah A SA Tuohey Laura L Liao Yang Y Shi Wei W Mullighan Charles G CG Farrar Michael A MA Nutt Stephen L SL Smyth Gordon K GK Zuber Johannes J Dickins Ross A RA

Genes & development 20140601 12

Loss-of-function mutations in hematopoietic transcription factors including PAX5 occur in most cases of B-progenitor acute lymphoblastic leukemia (B-ALL), a disease characterized by the accumulation of undifferentiated lymphoblasts. Although PAX5 mutation is a critical driver of B-ALL development in mice and humans, it remains unclear how its loss contributes to leukemogenesis and whether ongoing PAX5 deficiency is required for B-ALL maintenance. Here we used transgenic RNAi to reversibly suppre ...[more]

PMID: 24939936

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Project description:Many modern vaccines use defined adjuvants to stimulate the innate immune system and shape the adaptive immune response. The exact nature of these innate signals and whether immune differentiation can originate within the periphery is not known. In the present study we used an ovine lymphatic cannulation model to characterise the cellular and transcriptomic profile of the afferent lymph following injection of a liposomal vaccine formulation incorporating diphtheria toxoid and the innate stimulator poly (I:C) over a 78 h period. The response to this vaccine featured an early activation of broad proinflammatory pathways (e.g. TLR signalling and inflammasome pathways) and the transient recruitment of granulocytes into the lymph. At 24hrs a more monocytic cellular profile arose coinciding with a transition to a specific antiviral response characterised by the up-regulation of genes associated with the receptors typical for the viral mimic, poly (I:C) (e.g. TLR3, RIG-I and MDA5). At the latest time points the up-regulation of IL-17A and IL-17F suggested that Th17 cells may participate in the earliest adaptive response to this vaccine. Together these data provide the most comprehensive picture of the cellular and molecular mechanisms that link the periphery to the draining lymph node following vaccination and indicate that the immune response is capable of specialising within the periphery. This study employed an ovine model of pseudoafferent lymphatic cannulation (see de Veer et al. 2010, Vaccine) to characterise the innate immune response within the afferent lymph to vaccination with liposomes+poly (I:C)+ diptheria toxoid. The sheep used in this study had both their pre-femoral lymph nodes removed at 1 year of age. Approximately 1 year after the lymph node removal, a second surgery was performed to insert a 0.96_0.58mm heparin-coated polyvinyl chloride cannula into the pseudoafferent (previous efferent) lymphatic duct of both sides. At least seven days were allowed for healing to occur after surgery before vaccinations were administered and experimental lymph samples were collected. Handling of animals and experimental procedures were all approved by the Monash University Animal Ethics Committee in accordance with the relevant licensing agreement. Vaccinations were injected subcutaneously in the area drained by the prefemoral lymph node. Afferent lymphatic samples were collected prior to vaccination as a control (PRE) and at 4-6, 26-28, 51-53 and 76-78 hours post vaccination with liposomes+poly (I:C)+ diptheria toxoid. Lymphocytes were removed from the afferent lymph using immunomagnetic separation. Next-generation sequencing was performed on RNA derived from the remaining innate immune cells. Samples from three sheep were used at all time points except 4-6 and 26-28 hours, where only two samples yielded sufficient RNA for sequencing.

Dataset Information

Expression profiling of mouse bone marrow pre-B cells

Publications

Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia.

Similar Datasets

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