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SRP047387
Mus musculus
24 Downloadable Samples
Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM) that govern the delicate balance between HSC quiescence, self-renewal, and differentiation. It has been suggested that quiescent HSCs localize adjacent to BM arteriole endothelial cells in a significant and non-random distribution. This data suggests that the arteriole BM vascular niche may be the primary HSC niche. Because the BM arteriole niche is composed of tightly-associated pericytes, including smooth muscle actin+, LepR+, Nestin+, NG2+, and nonmyelinating Schwann cells, we sought to begin to uncouple the arteriole BM EC niche by examining its capacity to support the maintenance and expansion of HSCs ex vivo and in vivo. We developed a method to isolate and culture BM arteriole endothelial cells in serum-/growth factor-free conditions, allowing for a non-biased approach to examining their instructive function. Utilizing our protocol, we demonstrate that BM endothelial cells, but not BM stromal cells, have the capacity to expand long-term repopulating, multi-lineage HSCs in lieu of complex serum and cytokine supplementation. In addition, transplantation of arteriole endothelial cells promoted rapid hematopoietic recovery and protected HSCs following an LD50 dose of myeloablative irradiation. These data demonstrate that arteriole-derived BM endothelial cells are endowed with the necessary signals to support the self-renewal and regenerative capacity of LT-HSCs and that transplantation of arteriole BM endothelial cells could be used as a therapeutic means to decrease pancytopenias associated with myeloablative treatments to treat a wide array of disease states. Overall design: Transcriptome sequencing of bone marrow endothelial cells and bone marrow stroma, in vitro and in vivo, with and without HSC co-culture.
Publication Title
Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop because ECs are difficult to culture and little is known about how to sustain their vascular identity and direct them to form long-lasting new vessels or engraft into existing ones. We found that multiple non-vascular cell types transiently expressed EC markers after enforced expression of the transcription factors, Etv2, Erg, and Fli1. However, only mid-gestational amniotic cells could be converted to cells that maintained EC gene expression and proliferated in culture to yield billions of vascular cells. Even so, these converted cells performed sub-optimally in assays of EC function. We used constitutive Akt signaling to mimic the shear forces of the vascular environment and promote EC survival in an effort to correct the deficiencies of the converted cells. Akt signaling increased gene expression of EC morphogenesis genes, including Sox17, shifted the genomic targeting of Fli1 to favor nearby Sox consensus sites, and enhanced the in vivo vascular function of EC-like converted cells. Enforced expression of Sox17 was dispensable for broad EC gene activation, but indispensable for vascular engraftment and reperfusion of ischemic tissue. Our results identify a transcription factor network comprised of Ets and Sox17 factors that specifies and sustains endothelial cell fate and function. This work shows that the commonly used criterion of transcriptional similarity for cell conversion can fail to predict in vivo vascular function. Our approach shows that stringent functional testing in vitro and in vivo is necessary to validate engineered endothelial cell grafts. Overall design: Transcriptome sequencing of endothelial cells and amniotic cells
Publication Title
Sox17 drives functional engraftment of endothelium converted from non-vascular cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We have performed conditional inactivation of mef2c in the anterior heart field (AHF) of mice and observed a phenotypic spectrum of outflow tract anomalies in the conditional mutant hearts. In an effort to identify misregulated genes in the outflow tracts of the mutants, we have performed RNA-Seq on outflow tract samples dissected from E10.5 mutant and wild-type embryos. Overall design: There are four wild-type samples and four mutant samples.
Publication Title
MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
E47 represses Foxp3 transcription, albeit indirectly through the activation of unknown negative regulatory of Foxp3 transcription.
Publication Title
Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Endothelial cells from nine steady state tissues and two regenerating tissues (bone marrow and liver) were intravitally labeld, isolated via flow sorting, and immediately processed for RNA extraction.
Publication Title
Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. Overall design: Expression profiling by high throughput sequencing data; GPL17021 Illumina HiSeq 2500 (Mus musculus)
Publication Title
Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Microarray analysis was performed at the UHN Microarray Centre (UHNMAC, Ontario, Canada) using Illumina HumanHT-12 v4 BeadChip with 500 ng of total RNA prepared by RNeasy mini kit (QIAGEN, Cat. No. 74104). Samples from HCC1954 cells with 3-day treatment of TBK1-II at 4 uM were used to compare with vehicle-treated controls. Microarray data was processed and normalized by lumi package from BioConductor in R with Quantile Method. Difference between the samples were calculated by Bayesian statistic using limma package from BioConductor in R to obtain Moderated T value for subsequent Pathway analysis.
Publication Title
shRNA kinome screen identifies TBK1 as a therapeutic target for HER2+ breast cancer.
Sample Metadata Fields
Cell line
View Samples- Vitis vinifera, Vitis aestivalis
- 36 Downloadable Samples
- Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
we analyzed pathogen-induced changes in the transcriptome of Vitis vinifera Cabernet sauvignon and Vitis aestivalis Norton by conducting a large-scale study to measure transcript abundance at 0, 4, 8, 12, 24, and 48 hours post-treatment in conidiospore- and mock-inoculated leaves using Affymetrix GeneChip Vitis vinifera Genome Array
Publication Title
Powdery mildew induces defense-oriented reprogramming of the transcriptome in a susceptible but not in a resistant grapevine.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Background. Nuclear factor I-A (NFI-A), a phylogenetically conserved transcription/replication protein, plays a crucial role in mouse brain development. Previous studies showed that disruption of the Nfia gene in mice leads to perinatal lethality, corpus callosum agenesis, and hydrocephalus.
Publication Title
Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 18 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The study was designed to identify genes regulated after spinal transection that might contribute to regenerative growth of neurons projecting from the NMLF in Zebrafish.
Publication Title
Cysteine- and glycine-rich protein 1a is involved in spinal cord regeneration in adult zebrafish.
Sample Metadata Fields
Treatment, Time
View Samples