NPKLH data
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Mus musculus
SUBMITTER: Mechthild Lütge
PROVIDER: E-MTAB-8904 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The chemokines CXCL13 and CXCL12 are reported to be important for the germinal center reaction. Since CXCL12-deficient mice are embryonically lethal, here we took advantage of the Cxcl13-Cre/TdTomato mouse models to genetically ablate CXCL12 from B cell-interacting reticular cells and examine the molecular consequence on germinal center B cells. Spatial segregation of follicular dendritic cells, germinal center B cells and follicular helper T cells is impaired in Cxcl13-Cre/TdTomato Cxcl12fl/fl mice. Single cell transcriptomic analysis revealed that all germinal center B cell subsets (corresponding to distinct stages of the germinal center response) are present in draining lymph nodes of immunized CXCL12-conditionally deficient mice. While most transcriptional regulators of the germinal center response are unperturbed by the genetic perturbation of CXCL12, Bach2 levels were elevated in germinal center B cells from lymph nodes of Cxcl12fl/fl mice. Moreover, single cell B cell receptor sequencing revealed that germinal center B cells in Cxcl13-Cre/TdTomato Cxcl12fl/fl mice harbour a lower mutational burden when compared to germinal center B cells isolated from immunized control mice. Gene expression profiles were validated by flow cytometry and suggest that the provision of CXCL12 by reticular cells governs efficient germinal center responses.
2020-05-12 | E-MTAB-8454 | biostudies-arrayexpress
Project description:Efficient germinal center formation requires the coordinated movement of B cells between distinct regions of the B cell follicle where their fate and function is governed by the integration of cues from their interacting partners. While CXCL13 is known to be important for B cell chemoattraction and follicle formation, the molecular identity of B cell-interacting reticular cells remains ill-defined. Moreover, how CXCL13-expressing, B-cell interacting reticular cells are reprogramed to cater to the developing germinal center remains unclear. Here we use the Cxcl13-Cre/TdTomato mouse model to genetically target and decipher the cellular composition of lymph node CXCL13-expressing reticular cells under steady-state and inflammatory conditions. Moreover, we examine the consequence of cell-specific, genetic perturbation of CXCL12 on the molecular identity of the reticular cell network. Transcriptomic analyses revealed that B cell follicle reticular cell subset specification is predetermined in the steady-state, although additional transcriptional changes accompany germinal center formation. Although genetic perturbation of CXCL12 alters GC topology, the molecular identity of the underlying reticular cells remains largely unperturbed.
2020-05-12 | E-MTAB-8445 | biostudies-arrayexpress
Project description:Since the introduction of new generation pertussis vaccines, resurgence of pertussis is observed in many developed countries. Former whole-cell pertussis vaccines (wP) are able to protect against disease and transmission but have been replaced in several industrialized countries because of their reactogenicity and adverse effects. Current acellular pertussis vaccines (aP), made of purified proteins of Bordetella pertussis, are efficient at preventing disease but fail to induce long-term protection from infection. While the systemic and mucosal T cell immunity induced by the two types of vaccines has been well described, much less is known concerning B cell responses. Taking advantage of an inducible AID-Cre-EYFP fate-mapping mouse model, we sorted and analyzed by scRNAseq the transcriptomic profiles of memory B cells after a combination of prime:boost with the two classes of vaccines. B220+EYFP+GL7-PNA- memory B cells from the draining lymph nodes (dLNs) of tamoxifen-fed mice were FACS sorted 7 weeks after boost, alongside with B220+EYFP+GL7+PNA+ germinal center (GC) B cells and B220+GL7-PNA-EYFP-IgD+ naive B cells as a control population for the unsupervised clustering analysis. Single-cell mRNA sequencing was performed according to an adapted version of the SORT-seq protocol (Muraro et al., 2016, PMID: 27693023, with primers described in van den Brink et al. 2017), with cDNA libraries generation, sequencing and reads alignment performed at Single Cell Discoveries (Utrecht, Netherlands).
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Project description:The lymph node is home to resident macrophage populations that are essential for healthy immune function and homeostasis. They are involved in multiple processes including the initiation of the local response to pathogens, halting viral and bacterial spread, and clearance of apoptotic cells, but the macrophage niche and factors that create it are largely undefined. Here we analyse fibroblastic reticular cells (FRCs) as an essential component of the lymph node macrophage niche using single-cell RNA-sequencing. Our analysis revealed that most reticular cell subsets within lymph nodes expressed master macrophage regulator CSF1. We further show that signalling through CSF1R was sufficient to support macrophage development, while in the presence of LPS, FRCs underwent a mechanistic switch and maintained support through CSF1R-independent mechanisms. Our data reveal a critically important role for FRCs in the creation of the parenchymal macrophage niche within LNs.
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Project description:The tumor microenvironment (TME) is a complex mixture of tumor cells, immune cells, endothelial cells and fibroblastic stroma cells (FSC). While cancer-associated fibroblasts are generally seen as a tumor-promoting entity, it is conceivable that distinct FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intra-tumoral injection of a recombinant LCMV-based vaccine vector (r3LCMV) expressing the melanocyte differentiation antigen TRP2 results in T cell-dependent eradication of melanomas. Analysis of the TME revealed that viral vector transduction precipitates activation of particular FSC subsets. Using single-cell RNA-seq analysis, we identified a Cxcl13-expressing FSC population with a pronounced immune-stimulatory signature and increased expression of the inflammatory cytokine IL-33. Genetic ablation of Il33 in Cxcl13-Cre+ FSC impeded functionality of intratumoral T cells and consequently tumor control. Thus, reprogramming of distinct FSC subsets in the TME through LCMV-based vectors efficiently promotes tumor eradication by locally sustaining the activity of tumor-specific T cells.
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Project description:This SuperSeries is composed of the following subset Series: GSE38696: Gene expression in mouse germinal center light zone and dark zone B cells GSE38697: Gene expression in human germinal center light zone and dark zone B cells Keywords: Expression profiling by array Refer to individual Series
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Project description:Adrenal chromaffin cells and sympathetic neuron are derived from neural crest precursors and both cell types can give rise to childhood cancer, neuroblastoma. However only limited is known about the mechanism of their development. Better understanding of their transcriptomic profiles during development could gives an insight into the cell fates acquisition as well as the origin of neuroblastoma. Yellow fluorescent protein expressing sympathetic neuroblasts and adrenal chromaffin cells were isolated from E12.5 TH-IRES-Cre;ROSA26-EYFP mouse embryos by fluorescence-activated cell sorting. Transcriptomic profiles of sympathetic neuroblasts and adrenal chromaffin cells from embryonic age (E)12.5 TH-IRES-Cre;ROSA26-EYFP mice were generated by RNA sequencing, in four paired biological replicates.
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