Response of JHCO9 and JHOC5 cells to infection with NT (control) lentivirus or one of two knockdown lentiviruses, SPINK1 KD or IL-6 KD.
Targeting an autocrine IL-6-SPINK1 signaling axis to suppress metastatic spread in ovarian clear cell carcinoma.
Specimen part, Cell line
View SamplesFailures to produce neutralizing antibodies upon HIV-1 infection result in part from B cell dysfunction due to unspecific B cell activation. How HIV-1 affects antigen-specific B cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T cell - B cell immune synapse. This interference reduced B cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.
Specimen part
View SamplesWe describe GC-Tfr, a population of CD25 negative Foxp3 positive CXCR5hiPD1hiBCL6hi T-follicular regulatory cells that preferentially localise in the germinal centers. Male C57BL/6 Foxp3-DTR-GFP reporter mice were vaccinated with NP-Ova in Alum and 7 days later cells sorted before RNA-sequencing. Analysis revealed that GC-Tfr have a gene expression pattern equidistant between Tregs and Tfh, but fundamentally retain their suppressive characteristics as regulatory cells.
A distinct subpopulation of CD25<sup>-</sup> T-follicular regulatory cells localizes in the germinal centers.
Sex, Specimen part, Cell line
View SamplesT-follicular helper cells (Tfh) differentiate through a multistep process culminating in germinal center (GC) resident GC-Tfh that provide support to GC B-cells. T-follicular regulatory cells (Tfr) have been shown to have critical roles in the control of Tfh and germinal center formation. While Tfh cells are inhibited by IL-2, Treg cells depend on it. Here we describe a novel CD25 negative subset within both murine and human PD1+CXCR5+Foxp3+ Tfr that is preferentially located in the GC and can be clearly differentiated from non-GC Tfr, Tfh and effector Tregs by expression of a wide range of molecules. In comparison to Tfr and effector Tregs, GC-Tfr cells partially downregulate IL-2 dependent canonical Treg features, but retain suppressive function, while simultaneously upregulating genes associated with Tfh and GC-Tfh. We suggest that, similar to Tfh, Tfr follow a differentiation pathway culminating in a distinct GC resident subset, GC-Tfr.
A distinct subpopulation of CD25<sup>-</sup> T-follicular regulatory cells localizes in the germinal centers.
Sex, Age, Specimen part
View SamplesGene expression data from mouse organs after Advax injection
Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.
Sex, Specimen part
View SamplesEmbryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we perform a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identify components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we show in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming. Overall design: Examination of expression level changes at D0 and D2 MEFs
Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming.
No sample metadata fields
View SamplesEmbryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we perform a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identify components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we show in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming. Overall design: Examination of expression level changes in Gcn5 KO vs WT mESCs
Myc and SAGA rewire an alternative splicing network during early somatic cell reprogramming.
No sample metadata fields
View SamplesPeriostin participates in different processes involved in connective tissue homeostasis. It is also involved in repairment of damaged tissues. We used the osteoblast murine cell line MC3T3-E1 cell line to show how overexpresion of periostin is able to increase their adhesion properties while diminishing their migration capacity. By differential gene expression we evaluated putative targets involved in those cellular properties.
Role of Periostin in Adhesion and Migration of Bone Remodeling Cells.
Specimen part, Cell line
View SamplesGene expression data from mouse organs after hydroxypropyl--cyclodextrin injection
Hydroxypropyl-β-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen.
Sex, Specimen part
View SamplesWhsc1 gene codes for a SET domain-containing H3K36 dimethylase, whose activity has been suggested, in ex vivo cell culture experiments, to control many aspects of DNA and RNA processing (replication, repair, transcription, etc). Its precise function in vivo is still unclear. Here, we use RNA-seq transcriptome analysis to study the changes in gene expression in the absence of Whsc1. Our results show that, in the experimental system used, loss of Whsc1 caused massive changes in genes affecting many fundamental cellular processes, from cell cycle to ribosome synthesis, DNA repair, replication, etc. Overall design: Whsc1-KO mice are embryonic lethal. We therefore took hematopoietic cells from fetal liver of WT and Whsc1-KO embryo littermates and injected them in to lethally irradiated RAG1-KO recipients and allowed the generation of a full Whsc1-KO hematopoietic system. Then, WT and Whsc1-KO B cells were obtained from the spleen and stimulated with LPS to induce proliferation and class switch recombination. Flow cytometry and cell cycle analyses (among others) showed the existence of serious proliferative alterations in Whsc1-KO cells. Then, we performed paired-end RNAseq analyses of 7 independent WT and 6 independent Whsc1-KO biological replicates and we used these data to identify differentially expressed genes and pathways regulated by Whsc1 in B cells.
Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.
Cell line, Subject
View Samples