RNAseq of nestin-expressing murine brainstem progenitors infected with ACVR1 WT or R206H ACVR1 with and without H3.1K27M
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA516939 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8485370_1.fastq.gz | Fastqsanger.gz | |||
| SRR8485370_2.fastq.gz | Fastqsanger.gz | |||
| SRR8485371_1.fastq.gz | Fastqsanger.gz | |||
| SRR8485371_2.fastq.gz | Fastqsanger.gz | |||
| SRR8485362_1.fastq.gz | Fastqsanger.gz |
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Project description:Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, resulting in the death of 200-300 children each year in the United States. Recently it was discovered that approximately 25% of all DIPG cases harbor activating mutations in ACVR1, a gene that encodes Activin A receptor (ALK2), a receptor in the bone morphogenetic protein (BMP) pathway, and that DIPGs with ALK2 mutations commonly harbor an H3.1K27M mutation. Herein, we used the RCAS/TVA retroviral system to study the effects of ACVR1 mutations and H3.1K27M on DIPG pathogenesis. In vitro expression of R206H ACVR1 with and without H3.1K27M in nestin-expressing brainstem progenitors resulted in upregulation of mesenchymal markers and gene set enrichment analysis (GSEA) revealed Stat3 pathway activation. Neonatal expression of ACVR1 R206H or G328V in combination with H3.1K27M and p53 deletion in nestin-expressing brainstem progenitors induced glioma-like lesions expressing mesenchymal markers with Stat3 activation but was not sufficient for full gliomagenesis. In combination with platelet-derived growth factor A (PDGFA) signaling, ACVR1 R206H and H3.1K27M significantly decreased survival and increased tumor incidence. We demonstrate that targeting the BMP signaling pathway may be an effective therapeutic strategy to treat ACVR1 R206H mutant DIPGs. Exogenous Noggin expression at tumor initiation significantly increased tumor latency and treatment of ACVR1 R206H mutant murine DIPGs with LDN212854, an ACVR1 inhibitor, significantly prolonged their survival. We confirm relevance of our model to the human disease as human DIPG models with ACVR1 mutations were also sensitive to treatment with LDN212854 in vitro. Altogether, our studies demonstrate that ACVR1 R206H and H3.1K27M promote tumor initiation, accelerate gliomagenesis, promote a mesenchymal profile in part due to Stat3 activation, and identify LDN212854 as a promising compound to treat children with DIPG.
2019-01-25 | GSE125627 | GEO
Project description:Nestin-expressing progenitors (NEPs) of the developing cerebellum give rise to Bergmann glia, astrocytes and molecular layer interneurons via molecularly distinct subtypes. NEPs can be cultured in vitro as neurosphere in presence of growth factors. In order to characterise the primary neurosphere cultures generated from mouse and human developing cerebella, we performed single cell RNA-sequencing of primary NEP cultures established from 9-17 post-conception week human fetal cerebella and postnatal day 1 old mouse cerebella from two different mouse strains.
2025-12-04 | GSE301654 | GEO
Project description:scRNA-seq time course of cerebellar Nestin-expressing progenitors from neonatal mice with and without injury at birth
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Project description:Using the RCAS/tv-a system, we induced murine brainstem gliomas (PDGF-B; p53 loss using RCAS-Cre with and without H3.3K27M) in Nestin tv-a; p53 floxed mice
2017-05-11 | GSE98765 | GEO
Project description:H1299 cells were stably transfected with the Oct4 promoter/GFP or Nestin promoter/GFP reporter vectors. By FACS, 106 cells expressing high levels of GFP were isolated and placed into cell culture for twenty-four hours. Total RNA was used. Bone morphogenetic proteins (BMP) are aberrantly expressed in most lung carcinomas. BMPs mediate cell fate decisions and self-renewal of stem cells. Inhibition of BMP signaling decreases the growth and induces cell death of lung cancer cells lines. It is not known whether the BMP signaling cascade is growth promoting in lung cancer cells expressing the stem cell markers Oct4 and/or nestin. Lung cancer cells expressing Oct4 or nestin were isolated from lung cancer cell lines by stably transfecting the Oct4 promoter or Nestin promoter expression vectors that activate the green fluorescent protein reporter. Our studies support that lung cancer cells activating the Oct4 or nestin promoter are different cell populations. Microarray and quantitative RT-PCR demonstrated that the expression levels of specific stem cell markers were different between the isolated Oct4 and nestin cells. Both the Oct4 and nestin populations were more tumorigenic that controls but histologically they were quite different. The isolated Oct4 and nestin cells also responded differently to inhibition of BMP signaling. Blockade of BMP signaling with the BMP receptor antagonist DMH2 caused significant growth inhibition in both the Oct4 and nestin cell populations but only increased cell death in the nestin population. DMH2 also induced the expression of nestin in the Oct4 population but not in the nestin cells. We also show that BMP signaling is an important regulator of the inhibitor differentiation proteins Id1 and Id3 in Oct4 and nestin cell populations
2014-07-30 | GSE49281 | GEO
Project description:H1299 cells were stably transfected with the Oct4 promoter/GFP or Nestin promoter/GFP reporter vectors. By FACS, 106 cells expressing high levels of GFP were isolated and placed into cell culture for twenty-four hours. Total RNA was used. Bone morphogenetic proteins (BMP) are aberrantly expressed in most lung carcinomas. BMPs mediate cell fate decisions and self-renewal of stem cells. Inhibition of BMP signaling decreases the growth and induces cell death of lung cancer cells lines. It is not known whether the BMP signaling cascade is growth promoting in lung cancer cells expressing the stem cell markers Oct4 and/or nestin. Lung cancer cells expressing Oct4 or nestin were isolated from lung cancer cell lines by stably transfecting the Oct4 promoter or Nestin promoter expression vectors that activate the green fluorescent protein reporter. Our studies support that lung cancer cells activating the Oct4 or nestin promoter are different cell populations. Microarray and quantitative RT-PCR demonstrated that the expression levels of specific stem cell markers were different between the isolated Oct4 and nestin cells. Both the Oct4 and nestin populations were more tumorigenic that controls but histologically they were quite different. The isolated Oct4 and nestin cells also responded differently to inhibition of BMP signaling. Blockade of BMP signaling with the BMP receptor antagonist DMH2 caused significant growth inhibition in both the Oct4 and nestin cell populations but only increased cell death in the nestin population. DMH2 also induced the expression of nestin in the Oct4 population but not in the nestin cells. We also show that BMP signaling is an important regulator of the inhibitor differentiation proteins Id1 and Id3 in Oct4 and nestin cell populations Lung cancer cells expressing Oct4 or nestin were isolated and transfected with Oct4 or Nestin promoter expression vectors that activate the green fluorescent protein reporter. Microarray and quantitative RT-PCR were performed to study the differentially expressed genes. BMPs mediate cell fate decisions and self-renewal of stem cells were investigated.
2014-07-30 | E-GEOD-49281 | biostudies-arrayexpress
Project description:Diffuse midline glioma (DMG) is a type of lethal brain tumor that develops mainly in children. The majority of DMG harbor the K27M mutation in histone H3. Oligodendrocyte progenitor cells (OPCs) in the brainstem are candidate cells-of-origin for DMG, yet there is no genetically engineered mouse model of DMG initiated in OPCs. Here, we used the RCAS/Tv-a avian retroviral system to generate DMG in Olig2-expressing progenitors and Nestin-expressing progenitors in the neonatal mouse brainstem. PDGF-A or PDGF-B overexpression, along with p53 deletion, resulted in gliomas in both models. Exogenous overexpression of H3.3K27M had a significant effect on tumor latency and tumor cell proliferation when compared with H3.3WT in Nestin+ cells but not in Olig2+ cells. Further, the fraction of H3.3K27M-positive cells was significantly lower in DMGs initiated in Olig2+ cells relative to Nestin+ cells, both in PDGF-A and PDGF-B-driven models, suggesting that the requirement for H3.3K27M is increased when tumorigenesis is initiated in Nestin+ cells. Therefore, we need to find how the tumorigenic effects of H3.3K27M are more oncogenic in Nestin+ cells than Olig2+ cells.
2021-10-05 | GSE184934 | GEO
Project description:Purpose: The purpose of this study was to assess the effect of targeting the Acvr1G328V mutation to oligoendrocyte lineage cells, on gene expression in the brainstem of mice at postnatal day 7 Methods: Total RNA was extracted from the brainstem of postnatal day 7 Acvr1+/+;Olig2Cre/+ and Acvr1floxG328V/+;Olig2Cre/+ littermates, processed using the Illumina TruSeq Stranded Total RNA Sample Preparation kit, and subjected to deep sequencing. Results: A total of 247 genes were differentially expressed between the genotypes, with a corrected p value of less than 0.05. Of these genes, 125 were upregulated while 122 were downregulated. Many of the most downregulated genes were mature oligodendrocyte markers, while several genes that control oligodendrocyte progenitor formation and function were upregulated. Conclusions: The Acvr1G328V mutation causes differentiation arrest of oligodendroglial lineage cells.
2020-02-14 | GSE142776 | GEO
Project description:We report the application of RNA-sequencing for high-throughput profiling of gene expression in Nestin expressing cells of P5 mouse cerebellum Non-Irradiated or Irradiated at P1. By using the Nes-CFP reporter mouse line, we isolated Nes-CFP positive cells of P5 cerebellum to compare the transcriptomes between Nes-CFP positive cells from Non-irradiated cerebellum and cerebellum irradiated at P1.
2017-08-01 | GSE100941 | GEO
Project description:Diffuse midline glioma (DMG) is a type of lethal brain tumor that develops mainly in children. The majority of DMG harbor the K27M mutation in histone H3. Oligodendrocyte progenitor cells (OPCs) in the brainstem are candidate cells-of-origin for DMG, yet there is no genetically engineered mouse model of DMG initiated in OPCs. Here, we used the RCAS/Tv-a avian retroviral system to generate DMG in Olig2-expressing progenitors and Nestin-expressing progenitors in the neonatal mouse brainstem. PDGF-B overexpression, along with p53 deletion, resulted in gliomas. Exogenous overexpression of H3.3K27M had a significant effect on tumor latency and tumor cell proliferation when compared with H3.3WT in Nestin+ cells but not in Olig2+ cells. Further, the fraction of H3.3K27M-positive cells was significantly lower in DMGs initiated in Olig2+ cells relative to Nestin+ cells, suggesting that the requirement for H3.3K27M is reduced when tumorigenesis is initiated in Olig2+ cells. Interestingly, H3K27 trimethylation was decreased with H3.3K27M induction even in Olig2+ cells. Therefore, we need to find if there is transcriptional changes for the tumorigenesis with H3.3K27M in Olig2+ cells.
2021-10-05 | GSE184936 | GEO