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Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
Hippo signalling has been implicated as a key regulator of tissue regeneration. In the intestine, ex vivo organoid cultures model aspects of crypt epithelial regeneration. Therefore in order to uncover the Yap regulated transcriptional programs during crypt regeneration we performed RNA-sequencing of Yap wt and Yap deficient organoids, as well as organoids inducibly expressing Yap. Overall design: Yap loss of function organoids were harvested from Yapfl/fl;VillinCre mice (Yap-/-). In addition, we developed Yap overexpressing organoids by generating a doxycycline-inducible wild-type Yap transgenic line under the control of a Cre driven reverse tetracycline transactivator (rtTA), referred to here as YapTg. Organoids were seeded on day 0 from whole crypts isolated from Yap+/D, YapD/D, YapTg mice and cultured for 24 hours at which time they were harvested for transcriptome analysis by RNAseq.
Publication Title
Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer.
Sample Metadata Fields
No sample metadata fields
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SRP017101- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
Comparison of gene expresion profile of 4 SC clones and 4 SI clones at different time points defined a stabilization competency signiture required for successful reprogramming Overall design: mRNA profilling 4 SI clones at 5 time points, 4 SC clones at 6 time points, and 3 feeder samples.
Publication Title
A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Myelination is essential for nervous system function. Schwann cells interact with neurons and with the basal lamina to sort and myelinate axons, using known receptors and signaling pathways. In contrast, the transcriptional control of axonal sorting and the role of mechano-transduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. Here, we describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice we show that Taz is required in Schwann cells for radial sorting and myelination. Yap is redundant with Taz as ablation of both Yap and Taz abolishes radial sorting. Yap/Taz regulate Schwann cell proliferation and transcription of basal lamina receptors, both necessary for proper radial sorting of axons, and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells. Overall design: 3 cKO and 3 control wild-type mice
Publication Title
YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene regulatory networks that govern hematopoietic stem cells (HSC) and leukemiainitiating cells (L-IC) are deeply entangled. Thus, the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias.
Publication Title
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 189 Downloadable Samples
- Illumina HiSeq 3000
Description
The weekly turnover of the intestinal epithelium is driven by multipotent, Lgr5+, crypt base columnar cells (CBCs). In response to injury, however, Lgr5+ cells are lost but then re-emerge and are required for successful recovery. How these resurgent Lgr5+ stem cells arise is unclear. We transcriptionally profiled single cells from regenerating intestinal epithelia and identified a unique cell type we term the revival stem cell (rSC). rSCs are mutually exclusive to CBCs and are distinguished by elevated expression of cell survival and DNA repair genes. In homeostasis, rSCs are extremely rare, but nevertheless give rise to all the major cell types of the intestine including crypt-villus axes. After damage rSCs display a 20-fold, Yap-dependent, transient expansion, reconstitute the Lgr5+ CBC compartment and are required to regenerate a functional intestine. These studies define a unique stem cell phenotype that is mobilized by damage to reconstitute the intestinal epithelium. Overall design: Examination of regenerating mouse intestinal epithelium.
Publication Title
Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
We studied the effect of knowking down SUZ12 +/- knowckdown of BRM on the responsivness of IFNg stimulated genes. Cells were transfected with siSZU12+/-siBRM or control siRNA+/-siBRM. Cells were then left untreated or exposed to IFNg for 6 hours.
Publication Title
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
We studied the effect of reconstitution of BRG1 in BRG1-deficient cells on the responsivness of IFNg stimulated genes. Cells were infected with control adenovirus or BRG1-encoding virus. Cells were then left untreated or exposed to IFNg for 6 hours.
Publication Title
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In embryonic stem cell (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors that regulate the ESC state are not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 Ubiquitin Ligase Protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses revealed that MKRN1 is a novel RNA-binding protein that exists within messenger ribonucleoprotein (mRNP) complexes in undifferentiated ESC populations. In accordance with its presence in mRNPs, MKRN1 is mobilized to stress granules (SG) upon arsenite-induced stress, yet MKRN1 is not required for SG formation. RIP-chip analysis revealed that MKRN1 associates with mRNAs encoding functionally related regulatory proteins involved in diverse processes such as cell differentiation, apoptosis, or secreted proteins. Thus, our unbiased systems level analyses supports a role for MKRN1 as a novel RNA-binding protein and a potential gene regulatory protein within the ESC GRN.
Publication Title
Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network.
Sample Metadata Fields
Sex, Specimen part, Time
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