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SRP194327
Drosophila melanogaster
73 Downloadable Samples
Illumina HiSeq 2500
Description
Ageing populations pose one of the main public health crises of our time. Reprogramming gene expression by altering the activities of sequence-specific transcription factors (TF) can ameliorate deleterious effects of age. Here we explore how a circuit of TFs coordinates pro-longevity transcriptional outcomes, which reveals a multi-tissue and multi-species role for an entire protein family: the E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan by coordinating activation of Aop, an ETS transcriptional repressor, and Foxo, a Forkhead transcriptional activator. Aop and Foxo bind the same genomic loci, and we show that, individually, they effect similar transcriptional programmes in vivo. In combination, Aop can both moderate or synergise with Foxo, dependent on promoter context. Moreover, Foxo and Aop oppose the activities of Pnt, an ETS transcriptional activator, effecting a transcriptomic programme that correlates lifespan outcomes. Directly limiting Pnt extended lifespan, suggesting this is how Aop and Foxo promote longevity. The lifespan-limiting role of Pnt appears to be balanced by a requirement for metabolic regulation in young flies, in which the Aop-Pnt-Foxo circuit determines nutrient storage, and Pnt regulates lipolysis and responses to nutrient stress. Molecular functions are conserved amongst ETS TFs, suggesting others may also affect ageing. We show that Ets21C limits lifespan, functioning in the same genetic network as Foxo and IIS. Other ETS TFs appear to play roles in fly ageing in multiple contexts, since inhibiting the majority of the family in intestine, adipose or neurons extended lifespan. We expand the repertoire of lifespan-limiting ETS TFs in C. elegans, confirming their conserved function in ageing. Altogether this study reveals that roles of ETS TFs in physiology and lifespan are conserved throughout the family, both within and between species. Overall design: foxo, aopACT and pntP1 overexpression in S106 D. melanogaster, polyA RNAseq.
Publication Title
Longevity is determined by ETS transcription factors in multiple tissues and diverse species.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of bone marrow derived macrophages (BMDM) incubated with dexamethasone&IL4 (Dexa+IL4), B16F1 tumor conditioned medium (cmB16), and B16F1 tumor conditioned medium supplemented with dexamethasone&IL4 (cmB16+dexa+IL4). Results allow detection of genes that require synergistic stimulation of tumor factors and Th2 cytokines.
Publication Title
Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor-associated macrophages (TAMs) represent alternatively activated (M2) macrophages that support tumor growth. Previously, we have described a special LYVE-1(+) M2 TAM subset in vitro and in vivo; gene profiling of this TAM subset identified MS4A8A as a novel TAM molecule expressed in vivo by TAM in mammary carcinoma and malignant melanoma. In vitro, Ms4a8a mRNA and MS4A8A protein expression was strongly induced in bone marrow-derived macrophages (BMDMs) by combining M2 mediators (IL-4, glucocorticoids) and tumor-conditioned media (TCM). Admixture of MS4A8A(+) TCM/IL-4/GC-treated BMDM significantly enhanced the tumor growth rate of subcutaneously transplanted TS/A mammary carcinomas. Upon forced overexpression of MS4A8A, Raw 264.7 macrophage-like cells displayed a special gene signature. Admixture of these MS4A8A(+) Raw 264.7 cells also significantly enhanced the tumor growth rate of subcutaneously transplanted mammary carcinomas. To identify the signaling pathways involved in synergistic induction of MS4A8A, the major signaling cascades with known functions in TAM were analyzed. Although inhibitors of NF-B activation and of the MAPK JNK and ERK did not show relevant effects, the p38/ MAPK inhibitor SB203580 strongly and highly significantly (p > 0.001) inhibited MS4A8A expression on mRNA and protein level. In addition, MS4A8A expression was restricted in M2 BMDM from mice with defective GC receptor (GR) dimerization indicating that classical GR gene regulation is mandatory for MS4A8A induction. In conclusion, expression of MS4A8A within the complex signal integration during macrophage immune responses may act to fine tune gene regulation. Furthermore, MS4A8A(+) TAM may serve as a novel cellular target for selective cancer therapy.
Publication Title
Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 16 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Response of Saccharomyces cerevisiae strain BY4741 to desiccation
Publication Title
Phenomic and transcriptomic analyses reveal that autophagy plays a major role in desiccation tolerance in Saccharomyces cerevisiae.
Sample Metadata Fields
Time
View Samples