Depletion of Rad21 in murine bone marrow leads to enhanced self-renewal in vitro
The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9.
Specimen part
View SamplesCebpa is a gene known for its role in hematopoetic development. Though it is proven to be indispensible in myelopoesis, the details of the role played by Cebpa in dendritic cell development is fairly unknown. Steady state DC development can be modelled in vitro by treating Lin- HSPC with FLT3L.
TNFα Rescues Dendritic Cell Development in Hematopoietic Stem and Progenitor Cells Lacking C/EBPα.
Specimen part
View SamplesNotch1-IC, Notch2-IC or EBNA2 have been induced in a conditionally immortalized human B cell line (EREB2-5) in order to identify similar and unique target genes in B cells. CAT was used as a control.
Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells.
No sample metadata fields
View SamplesPeptide immunotherapy aims to specifically restore tolerance to the administered self-antigen and prevent autoimmunity without the perturbation of normal immune function. We have developed a dose escalation protocol for subcutaneous delivery of the MHC II-restricted myelin basic protein peptide analogue Ac1-9[4Y] to T cell receptor transgenic (Tg4) mice. Dose escalation allows safe administration of high doses of peptide, which effectively induces antigen-specific tolerance and suppresses the development of experimental autoimmune encephalomyelitis, a model for the human condition multiple sclerosis. CD4+ T cells isolated from treated mice are anergic and suppressive in vitro and respond to stimulation by secretion of the immunoregulatory cytokine IL-10. To understand the molecular changes occurring throughout the course of dose-escalation immunotherapy, we undertook microarray analysis of CD4+ T cells at different the stages of treatment, using Tg4 Rag-1 deficient mice, which lack naturally occurring regulatory T cells and have a monoclonal CD4+ T cell population
Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.
Specimen part, Treatment
View SamplesPreparation of exosomes isolated from semen contain a substantial amount of RNA, mostly from 20 to 100 nucleotides in length. We sequenced separately 20-40 and 40-100 nucleotide fractions of RNA from exosomes isolated from semenal fluid from six healthy donors. We found various classes of small non-coding RNA, including mature microRNA and piwi-RNA, as well as abundant Y RNAs and tRNAs present in both full length and fragmented forms. Specific RNAs were consistently present in all donors. For example, fifteen (of ~2,600 known) microRNAs constituted over 80% of mature microRNA in SE. Additionally, tRNA fragments were strongly enriched for 5’-ends of 18-19 or 30-34 nucleotides in length. Overall design: Size-fractionated small RNA profiles from exosomes isolated from the seminal fluid of six healthy donors
Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions.
No sample metadata fields
View SamplesLangerhans dendritic cells represent abundantly occuring and evolutionary highly conserved DCs specifically located in the stratified epithelial tissues. LCs are unique among DC family members in that they express epithelial-type adhesion molecules, allowing them to form a tight three-dimensional network in basal and suprabasal epidermal keratinocyte layers and developmentally dependent on the cytokine TGF-1. In the present study, we identified BMP-7 as another key factor inducing LC differnetiation. Here we have performed comparative analysis of highly purified CD207+/CD1a+ in vitro generated Langerhans cells in the presence of BMP-7 and TGF-1. We have identified that both BMP-7-LCs and TGF-1-LCs are closely related to each other.
Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation.
Specimen part, Treatment, Subject
View SamplesComplex regulatory mechanisms control continuous maintenance of myeloid progenitors and renewal of differentiated cells. Transcription factors play a important role in these processes. Here we report that the activation the calcineurin-NFAT signaling pathway inhibit the proliferation of myeloid granulocyte-monocyte progenitor (GMP). Myeloid progenitor subtypes possessed different susceptibilities to Ca2+ flux induction and consequently differential engagement of the calcineurin-NFAT pathway. This study show that inhibition of the calcineurin-NFAT pathway enhanced proliferation of GMPs both in vivo and in vitro. The calcineurin-NFAT signaling in GMPs is initiated through Flt3-L. The inhibition of the calcineurin-NFAT pathway altered the expression of the cell cycle regulation genes CDK4, CDK6, and CDKN1A, thus enabling faster cell cycle progression. The extensive use of NFAT inhibitors in the clinic should take into account that, in addition to the immunosuppression role in lymphoid cells, these NFAT inhibitors also affect the maintenance of the myeloid compartment.
Calcium and calcineurin-NFAT signaling regulate granulocyte-monocyte progenitor cell cycle via Flt3-L.
Specimen part
View SamplesHuman Th, Treg and Th and Treg together can induce monocytes differentiate into different myeloid cell population. We were trying to compare the transcriptome of these populations.
Human Regulatory Dendritic Cells Develop From Monocytes in Response to Signals From Regulatory and Helper T Cells.
Specimen part
View SamplesWorms that inherited the sperm genome lacking the repressive mark H3K27me3 (K27me3 M+P-) misexpress genes in their germlines when compared to genetically identitical worms that inherited the sperm genome with H3K27me3 (K27me3 M+P+). Overall design: Transcriptome profiles of hermaphrodite germlines from hybrid worms that inherited the sperm genome with H3K27me3 (4 replicates of K27me3 M+P+) vs without H3K27me3 (4 replicates K27me3 M+P-) to compare to 4 replicates of 'wildtype'.
Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans.
Specimen part, Cell line, Subject
View SamplesThe germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germline traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in C. elegans suggested that expression of germline genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s longevity. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knock-down of individual P-granule and other germline genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germline program to daf-2’s long lifespan, and also tested if other mutants known to express germline genes in their somatic cells are long-lived. Our key findings are: 1) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. 2) Whole-genome transcript profiling of animals lacking a germline revealed that germline transcripts are not up-regulated in the soma of daf-2 worms compared to the soma of control worms. 3) Simultaneous removal of multiple P-granule proteins or the entire germline program from daf-2 worms did not reduce their lifespan. 4) Several mutants that robustly express a broad spectrum of germline genes in their somatic cells are not long-lived. Taken together, our findings argue against the hypothesis that acquisition of a germ cell program in somatic cells increases lifespan and contributes to daf-2’s longevity. Overall design: Transcriptome profiles of 3 replicates of sterile daf-2; mes-1 double mutants (experimental) and 3 replicates of sterile mes-1 single mutants (control) grown at 24°C
Reevaluation of whether a soma-to-germ-line transformation extends lifespan in Caenorhabditis elegans.
Cell line, Subject
View Samples