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Global transcriptome of bone marrow Nestin+ mesenchymal stromal cells in homoestatis and human xenografts at early and late time points

ABSTRACT: Global transcriptome of bone marrow Nestin+ mesenchymal stromal cells in homoestatis and human xenografts at early and late time points

PROVIDER: PRJNA625220 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11541500_1.fastq.gz	Fastqsanger.gz
	SRR11541500_2.fastq.gz	Fastqsanger.gz
	SRR11541501_1.fastq.gz	Fastqsanger.gz
	SRR11541501_2.fastq.gz	Fastqsanger.gz
	SRR11541502_1.fastq.gz	Fastqsanger.gz

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Global transcriptome of bone marrow Nestin+ mesenchymal stromal cells in homoestatis and human xenografts at early and late time points

Project description:We analysed the transcriptional signature of bone marrow Nestin+ mesenchymal stromal cells extracted from the bone marrow of mice engrafted with human AML cell lines and compared it to the one of untransplanted mice

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RNAseq for Nestin+ bone marrow stromal cells in normal and MLL-AF9 mice

Project description:Cumulative evidence points out to the importance of the bone microenvironment for leukaemic development. Our preliminary results show that bone marrow stem cells, identified by the expression of the intermediate filament protein nestin (Nestin+ cells), provide support and chemoresistance to leukaemic cells. The rationale for these experiments is that leukaemic/Nestin+ cells crosstalk might regulate Nestin+ cells genetic profile to become more supportive elements for leukaemia. Nestin expression level distinguish two different Nestin+ populations, which seem to possess distint characteristics. Therefore, we would like to separately study high-expressing (Nestin high) and low-expressing Nestin cells (Nestin low). From our in vitro results, Nestin+ cells seem to be providing detoxifying tools to leukaemic cells such as antioxidant aminoacids and enzymes. The aim of the project is to identify pathways and genes differentially regulated in Nestin+ high and/or low cells in a leukaemic background.

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Global transcriptome of bone marrow niche cells in homoestatis and human xenografts at late time points

Project description:Global transcriptome of bone marrow niche cells in homoestatis and human xenografts at late time points

| PRJNA625216 | ENA

RNA-seq transcriptome analysis of Nestin-GFP-peri and -GFP-retic bone marrow stromal cells

Project description:Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSC in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging technique and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare Nestin-GFP-peri/NG2+ pericytes, distinct from sinusoid-associated Nestin-GFP-retic/LepR+ cells. The present RNA-seq study sought to obtain a comprehensive understanding of the differences between the two distinct HSC cellular niches. mRNA profiles of sorted Nestin-GFP-peri and -GFP-retic bone marrow stromal cells were generated from pooled mice in triplicate by Illumina HiSeq 2000 sequencing.

2013-10-10 | E-GEOD-48764 | biostudies-arrayexpress

RNA-seq transcriptome analysis of Nestin-GFP-peri and -GFP-retic bone marrow stromal cells

2013-10-10 | GSE48764 | GEO

Comparison between Nestin+ and Nestin- Ptch1 deficient GNPs

Project description:The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies.

2016-08-09 | GSE84392 | GEO

Comparison between Nestin+ and Nestin- Ptch1 deficient GNPs

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Dissection of cancer cell and stromal cell-derived signals in melanoma xenografts following treatment with the stromal-targeting agent DMXAA

Project description:5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1α/β, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1β, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-α, interferon-β and NFκB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition. Microarrays were used to identify separately the abundance of tumour cell and stromal cell RNA in A375 melanoma xenografts, with and without treatment by the stromal targetting drug DMXAA.

2012-03-15 | E-GEOD-26308 | biostudies-arrayexpress

Study of bone marrow Nestin+ mesenchymal stromal cells in control and leukemic mice

Project description:Study of bone marrow Nestin+ mesenchymal stromal cells in control and leukemic mice

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RNAseq for Nestin+ bone marrow stromal cells in normal and MLL-AF9 mice

Project description:RNAseq for Nestin+ bone marrow stromal cells in normal and MLL-AF9 mice

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