Filters
Technology
Platform
SRP161497
Mus musculus
10 Downloadable Samples
Illumina HiSeq 2500
Description
The Igf2 mRNA binding protein2/Imp2 was selectively deleted from adult mouse muscle; two phenotypes were observed: modestly decreased accrual of skeletal muscle mass after weaning and reduced wheel running activity but normal forced treadmill performance. Reduced voluntary activity occurs when fed a high fat diet but is normalized when consuming standard chow. The reduced muscle mass is due to diminished autocrine Igf2 production, reduced Akt1 activation, disinhibition of Gsk3a and reduced protein synthesis, without altered mTOR complex1 activity. The diet-dependent reduction in spontaneous exercise is accompanied by suboptimal muscle fatty acid oxidation, caused by reduced PPARa mRNA and protein, the former an Imp2 client. Nevertheless, in contrast to global Imp2 deficiency, muscle specific Imp2 inactivation does not alter glucose tolerance or the hypoglycemic effect of insulin. Imp2 deficiency in skeletal muscle reduces autocrine production of Igf2 and fiber growth and disorders nutrient metabolism so as to reduce voluntary physical activity. Overall design: The function of IMP2 in adult muscle has been investigated by creating the IMP2 muscle specific knockout mice. The metabolism of these mice at the whole body level, cellular lever, molecular level have been studied.
Publication Title
IMP2 Increases Mouse Skeletal Muscle Mass and Voluntary Activity by Enhancing Autocrine Insulin-Like Growth Factor 2 Production and Optimizing Muscle Metabolism.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. We show that YAP functions as a rheostat maintaining metabolic specialization, differentiation and quiescence within the hepatocyte compartment. Importantly, treatment with siRNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model (mice with liver-specific Mst1/Mst2 double knockout). Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of positional identity of hepatocytes, supports targeting YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype potentially responsive to this approach. Overall design: Mice with liver-specific Mst1/Mst2 double-knockout (Adeno-Cre injected Mst1-/-; Mst2Flox/Flox mice) were monitored for the formation of HCC by ultrasound imaging. Animals were then randomized to be treated by intravenous injection of either siYap-LNPs or siLuciferase-LNPs for a period of 9 days.
Publication Title
YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Aging at the cellular level is driven by changes in gene activity and epigenetic state that are only partially understood. We performed a comprehensive epigenomic analysis of the pancreatic ß cell, key player in glucose homeostasis and diabetes, in adolescent and very old mice. Globally, we observe a general methylation drift resulting in an overall more leveled methylome, suggesting that the maintenance of highly differential methylation patterns becomes compromised with advanced age. Importantly, we discover targeted changes in the methylation status of ß cell proliferation and function genes that go against the global methylation drift, are specific to ß cells, and correlate with repression of the proliferation program and activation of metabolic regulators. These targeted alterations frequently occur at distal cis-regulator elements, and are associated with specific chromatin marks and transcription factor occupancy in young ß cells. Strikingly, we find the insulin secretory response to glucose much improved in mature ß cells in mice, as predicted by the changes in methylome and transcriptome and in contrast to the decline in function observed in aged human ß cells. Thus, aging of terminally differentiated cells in mammals is not always coupled to functional decline. Overall design: RNA-seq was done on 3 biological replicas from old and three from young beta cells. each sample originated from a pool of 5-10 mic.e H3K27me3 ChIP-seq was done with two replicas for old mice (pool of 4-7 mice) and the rest of the ChIPseq (H3K4me1, H3K27ac and young H3K27me3) was sone with one sample (pool of few mice). BIS-seq was done on one sample from a pool of 10 young mice and one sample of a pool of old mice (18-22 months old)
Publication Title
Aging-Dependent Demethylation of Regulatory Elements Correlates with Chromatin State and Improved β Cell Function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
The sensory epithelium of cochleas and vestibules of mice were compared. The two tissues are quite similar in structure, but have distinct roles in hearing and balance. By comparing their gene expression, we hoped to identify key regulators of differentiation. Overall design: Cochlear and vestibular sensory epithelium was dissected from 20 inner ears of 10 P0 C57Bl/6J mice, generating 2.4 and 1.5 µg of total RNA, respectively. 450 ng RNA from each sample was used to create libraries with the TruSeq Stranded mRNA Sample Prep Kit (Illumina), followed by high-throughput sequencing at 100 bp paired end (PE) at the Technion Genome Center, Haifa, Israel. Six samples were generated, 3 cochlear and 3 vestibular, for sequencing in triplicate.
Publication Title
Computational analysis of mRNA expression profiling in the inner ear reveals candidate transcription factors associated with proliferation, differentiation, and deafness.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 384 Downloadable Samples
- Illumina HiSeq 2500
Description
The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-Seq method (scDual-Seq) that simultaneously captures both host and pathogen transcriptomes and use it to study the process of infection of individual mouse macrophages with the intracellular pathogen Salmonella typhimurium. Among the infected macrophages, we found three subpopulations and we show evidence for a linear progression through these subpopulations, supporting a model in which these three states correspond to consecutive stages of infection. Overall design: 96 single cells in 4 time point of infection (0,2.5,4,8 hours after infection)
Publication Title
scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 96 Downloadable Samples
- Illumina HiSeq 2500
Description
The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-Seq method (scDual-Seq) that simultaneously captures both host and pathogen transcriptomes and use it to study the process of infection of individual mouse macrophages with the intracellular pathogen Salmonella typhimurium. Among the infected macrophages, we found three subpopulations and we show evidence for a linear progression through these subpopulations, supporting a model in which these three states correspond to consecutive stages of infection. Overall design: 40 single cells, 6 ten cells bulk, 2 hundred cells bulk, in two time point of infection (0,4 hours after infection)
Publication Title
scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2500
Description
The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-Seq method (scDual-Seq) that simultaneously captures both host and pathogen transcriptomes and use it to study the process of infection of individual mouse macrophages with the intracellular pathogen Salmonella typhimurium. Among the infected macrophages, we found three subpopulations and we show evidence for a linear progression through these subpopulations, supporting a model in which these three states correspond to consecutive stages of infection. Overall design: a dilution series of mouse and salmonella RNA Please note that the samples are identical to GSM2729237-GSM2729241 and the RNA was extracted simultaneously. The only difference between them is the different protocol by which the libraries were made for sequencing (i.e. CEL-Seq2 or scDual-Seq).
Publication Title
scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We report a transcriptome comparison of HEK293 cells modified at the DPYSL2 gene promoter dinucleotide repeat (chr8:26,435,510-26,435,534) by CRISPR/Cas9 to change from the common 11 repeats to the more rare 13 repeats Overall design: 11/11 repeat HEK 293 cells were modified by CRISPR/Cas 9. Cell were flow sorted by the co-transfected GFP and single cells were expanded. From those we selected 4 modified and 8 unmodified clones for RNA seq. RNA was extracted at 80% confluency
Publication Title
The DPYSL2 gene connects mTOR and schizophrenia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Though Bcl11b has been previously considered a T-lineage identity transcription factor (TF) that restrains the innate-cell genetic programs, we report here that Bcl11b is highly expressed in mature ILC2s and acts upstream of the key ILC2 TFs Gfi1, Gata-3, and of IL-33 receptor IL1rl1 (T1ST2). Additionally, Bcl11b-/- ILC2s de-repressed Ror?t, Ahr and IL-23 receptor, normally expressed in type-3 ILCs (ILC3s). Consequently, Bcl11b-/- ILC2s lost ILC2 functions and gained ILC3 functions, expanding in response to the protease allergen papain, however producing IL-17 and IL-22, and not IL-5 and IL-13, causing lung neutrophilia rather than eosinophilia, and diminished mucus production. Our results broaden Bcl11b's role from a T-cell only TF, and establishes that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity through positive regulation of essential ILC2 TFs and negative regulation of pivotal ILC3 TFs. Overall design: RNA-seq analysis on sorted ILC2s from the mLNs of Bcl11bF/F Cre-ERT2 and wildtype mice at steady state following tamoxifen mediated deletion of Bcl11b
Publication Title
Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1113 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We successfully sequenced and annotated more than 400 cells from child, adult control, type 1 diabetes and type 2 diabetes donors. We detect donor-type specific transcript variation. We also report that cells from child donors have less defined gene signature. Cells from type 2 diabetes donors resemble juvenile cells in gene expression. Overall design: Cells from three adult controls (56, 74, 92), one donor with type 1 diabetes (91), two donors with type 2 diabetes (75, 143), and two child donors (40, 72) were sequenced. Numbers in parathesis indicates number of cells sequenced.
Publication Title
Single-Cell Transcriptomics of the Human Endocrine Pancreas.
Sample Metadata Fields
Specimen part, Subject
View Samples