Summary of Study ST002203

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001406. The data can be accessed directly via it's Project DOI: 10.21228/M80421 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002203
Study TitleSingle Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma
Study SummaryAbstract from manuscript Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting.
Institute
Brigham and Women's Hospital
DepartmentDepartment of Neurosurgery
LaboratoryNathalie Y.R. Agar
Last NameStopka
First NameSylwia
Address60 Fenwood Rd
Emailsstopka@bwh.harvard.edu
Phone617-525-9746
Submit Date2022-06-27
Raw Data AvailableYes
Raw Data File Type(s)imzML
Analysis Type DetailMALDI-MS
Release Date2022-07-15
Release Version1
Sylwia Stopka Sylwia Stopka
https://dx.doi.org/10.21228/M80421
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001406
Project DOI:doi: 10.21228/M80421
Project Title:Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma
Project Type:Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma
Project Summary:Abstract from manuscript Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting.
Institute:Brigham and Women's Hospital
Department:Department of Neurosurgery
Laboratory:Nathalie Y.R. Agar
Last Name:Stopka
First Name:Sylwia
Address:60 Fenwood Rd,
Email:sstopka@bwh.harvard.edu
Phone:617-525-9746

Subject:

Subject ID:SU002289
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id sample_id
SA211360mouse_CD73Dataset1
SA211361human_tumor_CD73Dataset2
Showing results 1 to 2 of 2

Collection:

Collection ID:CO002282
Collection Summary:As stated in the manuscript Frozen resection tissue from 9 glioblastomas, including 4 cases with high CD73 and 5 cases with low CD73 by IHC, were selected for MALDI MSI.
Sample Type:Brain

Treatment:

Treatment ID:TR002301
Treatment Summary:N/A

Sample Preparation:

Sampleprep ID:SP002295
Sampleprep Summary:As stated in the manuscript Frozen resection tissue from 9 glioblastomas, including 4 cases with high CD73 and 5 cases with low CD73 by IHC, were selected for MALDI MSI. Tissue was sectioned to 10 µm, thaw mounted onto indium-tin-oxide (ITO) slides, and serial sections were obtained for H&E staining. A high-resolution image of the whole H&E tissues was obtained through image stitching (Zeiss Observer Z.1, Oberkochen, Germany) using a plan-apochromat lens (20×) using an AxioCam MR3 camera. Matrix preparation of 1,5-diaminonaphthalene hydrochloride was prepared to a concentration of 4.3 mg/mL in 4.5/5/0.5 HPLC grade water/ethanol/1 M HCl (v/v/v). The matrix was sprayed using a TM-sprayer (HTX imaging, Carrboro, NC) with parameters of a flow rate (0.09 mL/min), spray nozzle velocity (1200 mm/min), spray nozzle temperature (75°C), nitrogen gas pressure (10 psi), track spacing (2 mm) and a four pass spray.

Combined analysis:

Analysis ID AN003606
Analysis type MS
Chromatography type None (Direct infusion)
Chromatography system Bruker
Column none
MS Type MALDI
MS instrument type FT-ICR
MS instrument name Bruker Solarix FT-ICR-MS
Ion Mode NEGATIVE
Units Da

Chromatography:

Chromatography ID:CH002665
Instrument Name:Bruker
Column Name:none
Chromatography Type:None (Direct infusion)

MS:

MS ID:MS003360
Analysis ID:AN003606
Instrument Name:Bruker Solarix FT-ICR-MS
Instrument Type:FT-ICR
MS Type:MALDI
MS Comments:Bruker software
Ion Mode:NEGATIVE
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