Filters
Technology
Platform
GSE75777
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pitx3 is a transcription factor that is expressed in all midbrain dopaminergic (mDA) neurons during early development, but later becomes restricted in dopaminergic subsets of substantia nigra compacta (SNc) and of the ventral tegmental are (VTA) that are vulnerable to neurodegenerative stress (MPTP, 6-OHDA, rotenone, Parkinson's disease). Overall, in mice, Pitx3 is required for developmental survival of ventral SNc neurons and for postnatal survival of VTA neurons (after postnatal day 40). With the aim of determining the gene networks that distinguish Pitx3-vulnerable (Pitx3-positive) from Pitx3-resistant (Pitx3-negative) subsets of SNc and VTA, we performed a comparison at the transcriptome level between FAC-sorted mDA neurons of SNc and VTA that were obtained from wild-type and Pitx3-/- newborn mice. The latter mice have already lost the majority of their TH+Calb1- mDA neurons of ventral SNc (Pitx3-dependent), but their TH+Calb1+ neurons of dorsal SNc (Pitx3-independent), including all of VTA neurons (50% are Pitx3-dependent and 50% Pitx3-independent), are unaffected by Pitx3 deletion. At postnatal day 40, Pitx3-/- mice display a marked loss of dopaminergic subsets of VTA that normally co-express Pitx3 and Calb1 (Pitx3-dependent neurons of VTA).
Publication Title
Rgs6 is required for adult maintenance of dopaminergic neurons in the ventral substantia nigra.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 4000
Description
NK cell development, maturation, and activation by cytokines is driven by alterations in gene expression mediated by activation and repression or transcriptional programs. In particular, we have extensively studied the role of STAT3 in human NK cells. This was based in part on a method we developed for in vitro expansion of large numbers of highly active NK cells using a genetically-modified feeder cell expressing 4-1BBL and membrane-bound IL-21. To dissect the various gene expression profiles induced by IL-21 from the various other signals received from the feeder cell, we purified peripheral NK cells from 4 healthy subjects (naïve, N), expanded NK cells for 14 days using CSTX002 feeder cells (expanded, E), and extracted RNA from the cells without (Neg) or after (Pos) the cells were activated with IL-21. We then performed RNA sequencing on each sample. Overall design: NK cells were purified from buffy coats obtained from 4 normal healthy blood-bank donors using RosetteSep NK for negative depletion of other cell subsets. NK cells were expanded by weekly stimulation with irradiated CSTX002 feeder cells. Naïve or expanded NK cells were stimulated for 30 minutes with 20 ng/ml recombinant human IL-21. Total RNA was prepared using the Total RNA Purification Plus Kit (Norgen Biotek, Ontario, ON, Canada). Libraries were prepared using the TruSeq RNA Sample Preparation Kit (Illumina Inc., San Diego, CA). 60–80 million paired-end 150 bp sequence reads per library were generated using the Illumina HiSeq4000 platform.
Publication Title
Efficient and Robust NK-Cell Transduction With Baboon Envelope Pseudotyped Lentivector.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
We investigated the RNA expression levels of NF-kB ligands and their receptors in epithelial cancer cells and cancer-associated fibroblasts (CAFs) from KPC tumors Overall design: We analysed 8 samples total (2 biological replicates. Each replicate with 2 conditions: DAPI- sorted cells (all live cells) and DAPI-CD45-CD31-EpCAM-PDPN+ sorted cells (CAFs). Each condition with 2 technical replicates.
Publication Title
IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 2500
Description
Recent pre-clinical and clinical evidences indicate that hematopoietic stem and progenitor cells (HSPCs) and/or their progeny can serve as vehicles for therapeutic molecule delivery across the blood brain barrier by contributing to the turnover of myeloid cell populations in the brain. However, the differentiation and functional characteristics of the cells reconstituted after transplantation are still to be determined, and in particular whether bona fide microglia could be reconstituted by the donor cell progeny post-transplant to be assessed. We here firstly demonstrate that HSPC transplantation can generate transcriptionally-dependable new microglia through a stepwise process reminiscent of physiological post-natal microglia maturation. Hematopoietic cells able to generate new microglia upon transplantation into myeloablated recipients are retained within human and murine long-term hematopoietic stem cells (HSCs). Similar transcriptionally dependable new microglia cells can also be generated by intra-cerebral ventricular delivery of HSPCs. Importantly, this novel route is associated to a clinically relevant faster and more widespread microglia replacement compared to systemic HSPC injection. Overall, this work supports the relevance and feasibility of employing HSPCs for renewing brain myeloid and microglia cells with new populations endowed with the ability to exert therapeutic effects in the central nervous system, and identifies novel modalities, such as transplantation of enriched stem cell fractions and direct brain delivery of HSPCs, for increasing the actual contribution of the transplanted cells to microgliosis and their therapeutic activity. Overall design: mRNA profiles of µ and TAµ myeloid brain populations were obtained in triplicate mice of Adult control, P10 control and Adult BU-treated mice after GFP Lin-transplantation (both µ and TAµ populations)
Publication Title
Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- NextSeq 500
Description
Hematopoietic Stem/Progenitor cells (HSPCs) are endowed with the role of maintaining a diverse pool of blood cells throughout the human life. Despite recent efforts, the nature of the early cell fate decisions remains contentious. Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured transcriptional landscape of hematopoietic differentiation. Still, this landscape misses important early fate decisions. We here provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands our understanding of the underlying structure of early adult human haematopoiesis. We also show that this map has strong similarities in topology and gene expression to that found in mouse. Finally, we identify the sialomucin CD164, as a reliable marker for the earliest branches of HSPCs specification and we showed how its use can foster the design of alternative transplantation cell products. Overall design: Single-cell mRNA sequencing of freshly isolated hematopoietic progenitors from human bone marrow. Sample HSC (Donor A) represents 1282 single cells. Sample MPP (Donor A) represents 215 single cells. Sample MLP (Donor A) represents 123 single cells. Sample PreB/NK (Donor A) represents 592 single cells. Sample MEP (Donor A) represents 1211 single cells. Sample CMP (Donor A) represents 1576 single cells. Sample GMP (Donor A) represents 1012 single cells. Sample Lin-CD34+CD164+ (Donor B) represents 6343 single cells. Sample Lin-CD34-CD164high (Donor B) represents 4434 single cells. Sample Lin-CD34lowCD164high (Donor B) represents 4266 single cells. Sample Lin-CD34-CD164low (Donor B) represents 358 single cells.
Publication Title
A comprehensive single cell transcriptional landscape of human hematopoietic progenitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Here we show that platinum-resistant ovarian cancer cells also show reduced cholesterol biosynthesis, and mostly rely on uptake of exogenous cholesterol for their needs. Expression of FDPS and OSC, enzymes involved in cholesterol synthesis, are decreased both in drug-resistant cells and upon TRAP1 silencing, whereas the expression of LDL receptor, the main mediator of extracellular cholesterol uptake, is increased. Strikingly, treatment with different statins to inhibit cholesterol synthesis reduces cisplatin-induced apoptosis, whereas silencing of LIPG, an enzyme involved in lipid metabolism, increases sensitivity to the drug.
Publication Title
Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Rationale: Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease by whole-lung transcriptome analysis. Methods: Wildtype mice were experimentally exposed to S. mansoni ova by intraperitoneal sensitization followed by tail vein augmentation, and the phenotype assessed by right ventricular catheterization and tissue histology, RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, the latter analyzed using 2 bioinformatic methods. Functional testing of the candidate IL-6 pathway was determined using IL6-knockout mice and the STAT3 inhibitor STI-201. Results: Wild-type mice exposed to S. mansoni had increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole lung transcriptome analysis identified the IL6-STAT3-NFATc2 pathway as being upregulated, which was confirmed by PCR and immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL6 or treated with STI-201 developed pulmonary hypertension associated with significant intima remodeling after exposure to S. mansoni. Conclusions: Whole lung transcriptome analysis identified upregulation of the IL6-STAT3-NFATc2 pathway, and IL6 signaling was found to be protective against Schistosoma-induced intimal remodeling.
Publication Title
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 183 Downloadable Samples
- Illumina HiSeq 2000
Description
Heterogeneity of meningeal cortical cells was deciphered on the molecular level using single cell RNA seq Overall design: RNA sequencing of 179 meningeal cortical cells isolated from naive wild-type mice
Publication Title
Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
White adipose tissue is primary involved in the response to insulin after feeding, while brain is not directly sensitive to insulin levels.
Publication Title
eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription.
Sample Metadata Fields
Specimen part
View Samples