AD drug discovery has rarely been addressed in the context of aging even though sporadic AD accounts for 99% of the cases. Phenotypic screens based upon old age-associated brain toxicities were used to develop the potent AD drug candidate J147. Here, we hypothesized that J147 would be effective against both brain aging and AD-associated pathology in rapidly aging SAMP8 mice, a model for early sporadic AD. An inclusive and integrative multi-omics approach was used to investigate protein expression, RNA expression, metabolite levels as well as cognition in old and young SAMP8 mice. J147 not only reduced the cognitive deficits and associated metabolic changes observed in old SAMP8 mice, it restored the levels of multiple markers of AD, vascular pathology, synaptic function, and inflammation to those approaching the young phenotype. Our data show that a drug candidate selected upon the basis of preventing old age-related brain toxicities also reduces AD-associated pathology. Overall design: The aim of this project was to investigate whether the AD drug candidate J147 protects SAMP8 mice from aging and AD-associated pathology and to assay the associated metabolic changes. Three three-month old male SAMP8 mice were fed with vehicle diet and three three-month old male SAMP8 mice with J147 diet until they reached ten months old. Four three-month old male SAMP8 mice were used as young control group.
A comprehensive multiomics approach toward understanding the relationship between aging and dementia.
No sample metadata fields
View SamplesIn this study we have analyzed the global gene expression of nave mouse embryonic stem cells in different culture conditions including R2i (PD0325901+SB431542), 2i (PD0325901+CHIR99021), and also PD0325901+LIF and SB431542+LIF to show the similarities and differences between the conditions in maintaining pluripotency.
Inhibition of TGFβ signaling promotes ground state pluripotency.
Specimen part, Cell line
View SamplesLong-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling).
Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel.
Specimen part, Disease
View SamplesSpatial localization is a key determinant of cellular fate and behavior, but spatial RNA assays traditionally rely on staining for a limited number of RNA species. In contrast, single-cell RNA-seq allows for deep profiling of cellular gene expression, but established methods separate cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos, inferring a transcriptome-wide map of spatial patterning. We confirmed Seurat’s accuracy using several experimental approaches, and used it to identify a set of archetypal expression patterns and spatial markers. Additionally, Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems. Overall design: We generated single-cell RNA-seq profiles from dissociated cells from developing zebrafish embryos (late blastula stage - 50% epiboly)
Spatial reconstruction of single-cell gene expression data.
Subject
View SamplesSMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesWild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesWild type, pkl, pkr2 and pkl pkr2 plants were grown, and gene expression in roots was compared at the age of 5 days. <br></br>
CHD3 proteins and polycomb group proteins antagonistically determine cell identity in Arabidopsis.
Age, Specimen part, Time
View SamplesWild-type and MZoep zebrafish embryos were mechanically dissociated and profiled using 10x Genomics pipeline. Overall design: 10x scRNA-seq was performed on visually staged, mechanically dissociated embryos. Samples were combined and sequenced in one batch.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesDendritic cells (DC) arise from a diverse group of hematopoietic progenitors and have marked phenotypic and functional heterogeneity. We have found previously that activation of protein kinase C beta 2 (PRKCB2) by cytokines or phorbol esters drives normal human CD34(+) hematopoietic progenitors and myeloid leukemic blasts (KG1, K562 cell lines, and primary patient blasts) to differentiate into DC, but the genetic program triggered by PRKCB2 activation that results in DC differentiation is only beginning to be characterized. Of the cPKC isoforms, only PRKCB2 was consistently activated by DC differentiation-inducing stimuli in normal and leukemic progenitors. To examine early changes in gene expression following PRKCB2 activation, we employed the following cell lines: (1) the CD34(+) human acute myeloid leukemia derived cell line KG1, which undergoes DC differentiation following phorbol ester treatment; (2) KG1a, a spontaneously arising differentiation-resistant daughter cell line of KG1 that has lost PRKCB2 expression; (3) clones established from KG1a that stably express exogenous PRKCB2-GFP fusion proteins and are once again able to undergo DC differentiation (KG1a-PRKCB2-GFP Clone E9 and Clone E11). We examined changes in gene expression in these cells following treatment with the phorbol ester PMA (phorbol 12-myristate 13-acetate) for 2 hours. Since KG1 and KG1a differ in PRKCB2 expression but have similar expression of the other protein kinase C isoforms, this protocol will allow for the identification of genes regulated by PRKCB2 activation.
Tumor-induced STAT3 signaling in myeloid cells impairs dendritic cell generation by decreasing PKCβII abundance.
Sex, Age, Specimen part, Cell line, Treatment
View SamplesPhospho-ribosome associated RNAs were immunopurified using the antibodies against phospho-S6. The purified RNAs were converted to cDNAs, which were sequenced in Illumina HiSeq platform. Vomeronasal organs were extracted from male CD-1 animals exposed to either pup cues or fresh bedding. Overall design: Total of 6 samples, 2 conditions and 3 replicates
Multisensory Logic of Infant-Directed Aggression by Males.
Sex, Specimen part, Cell line, Subject
View Samples