We develop a new ChIpseq method (iChIP) to profile chromatin states of low cell number samples. We use IChIP to profile the chromatin dynamics during hematopoiesis across 16 different cell types which include the principal hematopoietic progenitors Overall design: 3'' RNA-seq for digital gene expression quantitation across multiple cell types.
Immunogenetics. Chromatin state dynamics during blood formation.
No sample metadata fields
View SamplesPD-1 immune checkpoint blockade provides significant clinical benefits for cancer patients. However, factors influencing innate sensitivity remain incompletely catalogued. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies. Mutations in cell adhesion genes and the DNA repair gene BRCA2 were enriched in responding tumors, and a high mutational load associated with improved survival. Innately resistant tumors displayed frequent transcriptomic up-expression of genes that enriched for mesenchymal transition, cell adhesion, ECM organization, wound-healing and angiogenesis. The transcriptomes of innate resistance also enriched for signatures indicating up-regulation of these processes. Notably, MAPK-targeted therapy (MAPKi) induced similar signatures in melanoma, suggesting that a form of MAPKi resistance mediates cross-resistance to anti-PD-1 therapy. Co-enrichment of IPRIM (Innate anti-PD-1 Resistance Induced by MAPKi) signatures defined a transcriptomic subset across advanced cancers, suggesting that attenuating processes underlying these signatures may augment anti-PD1 responses. Thus, multi-factorial determinants influence anti-PD-1 patterns in melanoma. Overall design: Melanoma biopsies pre-anti-PD-1 therapy were sent for transcriptomic analysis by paired-end RNAseq analysis to find the correlates of response vs. non-response to the therapy
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.
No sample metadata fields
View SamplesSteer liver transcriptome
Differential expression of genes related to gain and intake in the liver of beef cattle.
Sex, Specimen part
View SamplesThe identification of a marker that is expressed in the conjunctival epithelium but not in the corneal epithelium has been a growing need. A more specific marker of limbal and conjunctival epithelia would be necessary to detect non-corneal epithelial cells on the corneal surface. To search for conjunctival specific marker(s), we first performed preferential gene profiling in the conjunctiva in direct comparison to that in the cornea using microarray technique.
Keratin 13 is a more specific marker of conjunctival epithelium than keratin 19.
Specimen part
View SamplesGoal was to identify yeast genes whose expression changed as a function of the shift from growth in bulk culture to growth in an air-liquid interfacial biofilm.
Ethanol-independent biofilm formation by a flor wine yeast strain of Saccharomyces cerevisiae.
Specimen part
View SamplesStem cell biology has garnered much attention due to its potential to impact human health through disease modeling and cell replacement therapy. This is especially pertinent to myelin-related disorders such as multiple sclerosis and leukodystrophies where restoration of normal oligodendrocyte function could provide an effective treatment. Progress in myelin repair has been constrained by the difficulty in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but significant advances are currently hindered by heterogeneous differentiation strategies that lack reproducibility. Here we provide a platform for the directed differentiation of pluripotent mouse epiblast stem cells (EpiSCs) through a defined series of developmental transitions into a pure population of highly expandable OPCs in ten days. These OPCs robustly differentiate into myelinating oligodendrocytes both in vitro and in vivo. Our results demonstrate that pluripotent stem cells can provide a pure population of clinically-relevant, myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development, drug screening, and potential cell-based remyelinating therapies.
Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells.
No sample metadata fields
View SamplesCell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphologyical and global gene expression profile molecular features consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into induced multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelinmyelinating axons both in vitro and in vivo. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.
Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells.
Specimen part, Treatment
View SamplesComparison of gene expression profiles from C. elegans wildtype strain (N2) treated with L4440 and T25B9.1 RNAi for 5 days after L4 larvae stage. Jena Centre for Systems Biology of Ageing - JenAge (ww.jenage.de) Overall design: 6 samples in 2 groups: N2, L4440 5 days (3 Samples); N2, T25B9.1 5 days (3 Samples)
Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesSelective genetic ablation of the SIRT1 deacetylase domain in skeletal muscle results in increased H4K16 acetylation and deregulated activation of the myogenic program in satellite cells Overall design: To establish the role of the deacetylase SIRT1 in skeletal muscle we examined the genome wide distribution of H4K16ac in quiescent (FI) and proliferating (Cul) satellite cells isolated from WT mice (C57Bl/6 background) and SIRT1mKO (generated via breeding of Pax7cre/+ knock-in mice with mice containing the floxed exon 4 SIRT1 allele). We also analyzed the distribution of SIRT1 in quiescent and proliferating FACS isolated WT satellite cells (two replicates). We generated the mRNA profiles (at least two replicate for each experiment) of FACS isolated quiescent, proliferating and differentiating (1 day in differentiation medium) satellite cells of WT mice and SIRT1mKO. The selective genetic ablation of the SIRT1 deacetylase domain in skeletal muscle results in increased H4K16 acetylation and deregulated activation of the myogenic program.
The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells.
No sample metadata fields
View SamplesTo better understand the mechanistic basis of aging and its relationship with retinal degeneration, we examined gene expression changes in aging rod photoreceptors. Rod photoreceptor cell death is a feature of normal retinal aging and is accelerated in many retinal degenerative diseases, including AMD, the leading cause of untreatable adult blindness in the United States and other western countries. To our knowledge, the examination of age-related gene expression changes in a specific neuronal cell-type is novel, and it has allowed us to identify significant age-related changes with better resolution than is possible with whole retina samples. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR. Our results suggest that aging is progressive, beginning even in young adult mice. Although rod photoreceptors are highly specialized neurons, our analyses revealed changes in consensus pathways of aging, including oxidative phosphorylation and stress responses affecting transcription and inflammation. In addition, we identified stress response processes that may be especially relevant for the aging retina and retinal diseases, such as angiogenesis and nuclear receptor signaling pathways that affect retinoid and lipid metabolism.
Distinct signature of altered homeostasis in aging rod photoreceptors: implications for retinal diseases.
Age, Specimen part
View Samples