Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA693800 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13496726_1.fastq.gz | Fastqsanger.gz | |||
| SRR13496726_2.fastq.gz | Fastqsanger.gz | |||
| SRR13496727_1.fastq.gz | Fastqsanger.gz | |||
| SRR13496727_2.fastq.gz | Fastqsanger.gz | |||
| SRR13496728_1.fastq.gz | Fastqsanger.gz |
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Project description:Brain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor cells (HSPCs) within tumor tissues that are positively linked to glioblastoma malignancy. In contrast to the medullary hematopoietic compartment, tumor-associated HSPCs are comprised of a majority of CD38- immature cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display patterns of accelerated cell cycle. When cultured ex vivo, tumor-associated HSPCs form prevalently myeloid colonies, suggesting potential in situ myelopoiesis. In experimental models, HSPCs promote tumor cell proliferation, expression of the immune checkpoint PD-L1 and secretion of tumor promoting cytokines such as IL-6, IL-8 and CCL2, indicating concomitant support of both malignancy and immunosuppression. Additionally, the frequency of tumor-associated HSPCs is prognostic for patient survival and correlate with immunosuppressive phenotypes. These findings identify a new element in the complex landscape of glioblastoma that may serve as an independent prognostic factor or target for brain tumor immunotherapies.
2021-05-25 | GSE165238 | GEO
Project description:Brain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor cells (HSPCs) within glioblastoma tissues. Furthermore, we demonstrate a positive link of tumor-associated HSPCs with malignant and immunosuppressive phenotypes. Compared to the medullary hematopoietic compartment, tumor-associated HSPCs contain a higher fraction of immunophenotypically and transcriptomically immature, CD38- cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display signatures of active cell cycle phases. When cultured ex vivo, tumor-associated HSPCs form myeloid colonies, suggesting potential in situ myelopoiesis. In experimental models, HSPCs promote tumor cell proliferation, expression of the immune checkpoint PD-L1 and secretion of tumor promoting cytokines such as IL-6, IL-8 and CCL2, indicating concomitant support of both malignancy and immunosuppression. In patients, the amount of tumor-associated HSPCs in tumor tissues is prognostic for patient survival and correlates with immunosuppressive phenotypes. These findings identify an important element in the complex landscape of glioblastoma that may serve as a target for brain tumor immunotherapies.
| S-EPMC8222381 | biostudies-literature
Project description:Ageing-associated proteome and acetylome of hematopoietic progenitor cells
2020-09-24 | PXD021651 |
Project description:Hematopoietic progenitor cells
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Project description:Hematopoietic progenitor kinase 1 (HPK1), a hematopoietic cell-specific Ste20-related serine/threonine kinase, is a negative regulator of signal transduction in immune cells, including T cells, B cells, and dendritic cells (DCs). In mice, HPK1 deficiency subverts inhibition of the anti-tumor immune response and is associated with functional augmentation of anti-tumor T cells. We have used a potent, small molecule HPK1 inhibitor, Compound 1, to investigate the effects of pharmacological intervention of HPK1 kinase activity in immune cells. Compound 1 enhanced Th1 cytokine production in T cells and fully reverted immune suppression imposed by the prostaglandin E2 (PGE2) and adenosine pathways in human T cells. Moreover, the combination of Compound 1 with pembrolizumab, a humanized monoclonal antibody against the programmed cell death protein 1 (PD-1), demonstrated a synergistic effect, resulting in enhanced interferon (IFN)-γ production. Collectively, our results suggest that blocking HPK1 kinase activity with small molecule inhibitors alone or in combination with checkpoint blockade may be an attractive approach for the immunotherapy of cancer.
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Project description:Quantitative proteomic analysis of mouse fetal and adult hematopoietic progenitor cells using TMT6plex and an SPS-MS3 method.
2020-07-02 | MSV000085672 | MassIVE
Project description:Human iPSC-derived cerebral organoids reveal progenitor pathology in EML1-linked cortical malformation
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Project description:Glioblastoma (GBM) is the most common and aggressive primary brain tumor with limited therapeutic options, possibly because of the highly tumorigenic subpopulations of stem cell-like cells. Mechanisms that sustain cancer stem cells are crucial to tumor progression. The polycomb group protein BMI1 (BMI1 proto-oncogene, polycomb ring finger) maintains cancer hallmarks including the glioblastoma stem-like cell (GSC) state. Ubiquitin-specific protease 22 (USP22) is highly expressed in and required for the maintenance of cancer stem cells (CSCs). Previously, we observed that forced expressed microRNA-218 in glioblastoma cells led to suppressed BMI1 expression. However, the pathways engaged by USP22 or driving BMI1 accumulation in GSCs remained elusive. Here, we found USP22 to be a novel deubiquitylase of BMI1. USP22 directly deubiquitylates and stabilizes BMI1. USP22 protein levels are elevated in tumor neurosphere. USP22 depletion induces BMI1 destabilization, and results in the inhibition of GSCs self-renewal by regulating a broad range of genes involved in glioma stemness and progression. Xenograft analyses using U87MG cells showed that both USP22 and BMI1 depletion attenuated tumor growth. Clinically, the expression levels of USP22 and BMI1 were positively correlated with those common targets like POSTN, HEY2, or PDGFRA and inversely correlated with ATF3 in human glioblastoma specimens. Taken together, our data reveals that USP22 functions as a novel deubiquitylase of BMI1 and inhibits self-renewal of GSCs by stabilizing BMI1. These findings also indicate that the USP22-BMI1 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioblastoma.
2017-01-01 | GSE89239 | GEO
Project description:An optimized whole genome bisulfite sequencing protocol (µWGBS, Farlik et al. 2015 Cell Reports) was used to establish DNA methylation profiles of FACS-purified stem and progenitor cells types of the human blood lineage. Most cell types were sorted from the peripheral blood of three donors with eight pools of ten cells, two pools of 50 cells, and one pool of 1000 cells. HSCs and MPPs were also sorted from fetal liver (HSCs only), cord blood, and bone marrow. Single-cell methylomes using the scWGBS protocol (Farlik et al. 2015 Cell Reports) were established for six cell types (HSC, MPP, CMP, GMP, CLP, MLP0). Gene expression profiling using the Smart-seq2 protocol (Picelli et al. 2013 Nature Methods) was done for nine stem/progenitor cell types (HSC, MPP, CMP, GMP, CLP, MLP0, MLP1, MLP2, MLP3).
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Project description:Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, among the IDH1/2-wildtype patients, tumors from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. We performed genome- and/or transcriptome-wide molecular profiling of primary tumor samples from 70 glioblastoma patients of the German Glioma Network, including 23 longterm survivors with >36 months overall survival (OS), 16 short-term survivors with <12 months OS, and 31 patients with intermediate OS For this study, we screened prospectively recruited patients with a histopathological reference diagnosis of glioblastoma, known KPS at diagnosis, information on extent of resection by early postoperative neuroimaging, available frozen tissue specimens from the initial operation, and documented clinical outcome.
2014-03-27 | E-GEOD-53733 | biostudies-arrayexpress