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Vidhya M.
Ravi et al.
of the Research Laboratory of Microenvironment and Immunology at the University Medical Center Freiburg, Germany, characterized glioblastoma by spatially resolved transcriptomics, metabolomics and proteomics; Deciphering transcription procedures shared between regions between patients, inferring that glioblastoma is spatially isolated tissue in lineage states and adapts to inflammatory or metabolic stimuli for reactive transformation
to mature astrocytes.
The results were published online in the June 2022 issue of Cancer Cell
.
- Excerpted from the article chapter
【Ref: Ravi VM, et al.
Cancer Cell.
2022 June 13; 40(6):639-655.
e13.
doi: 10.
1016/j.
ccell.
2022.
05.
009.
】
Research background
Glioblastoma (GBM) is a malignant tumor of the central nervous system characterized by subclonal diversity and moderately developed dynamic adaptation
.
The mechanism of dynamic recombination against the spatial background of this tumor remains undetermined
.
Vidhya M.
Ravi et al.
of the Research Laboratory of Microenvironment and Immunology at the University Medical Center Freiburg, Germany, characterized glioblastoma by spatially resolved transcriptomics, metabolomics and proteomics; Deciphering transcription procedures shared between regions between patients, inferring that glioblastoma is spatially isolated tissue in lineage states and adapts to inflammatory or metabolic stimuli for reactive transformation
to mature astrocytes.
The results were published online in the June 2022 issue of Cancer Cell
.
Research methods
.
Inferring copy number changes and emphasizing subclonal spatial cohesion associated with reactive transcription procedures confirms that environmental pressures cause selection pressures
.
Glioblastoma stem cell models were implanted into human and rodent neocortical tissues to mimic various environments to show that transcriptional states stem from dynamic adaptation
to various environments.
Provides a map
of the spatially resolved transcription procedures and cellular interactions of glioblastoma with its local microenvironment.
Single-cell technology was used to analyze the transcriptional regulation and dynamic evolution
of single cells in healthy human brains and malignant tumors.
Single-cell RNA sequencing (scRNA-seq) studies of high- and low-grade gliomas have shown that intratumor heterogeneity and dynamic plasticity across cellular states are hallmarks
of malignant brain tumors.
This dynamic adaptation occurs in four different states, mes-like, NPC-like, AC-like, and oligodendroid precursor (OPC-like), reflecting the early development
of a healthy human brain.
Brain tumors exhibit transcriptional adaptations and evolutions similar to healthy brains, but have long been considered a separate entity, ignoring the role of
the local microenvironment in tumorigenesis.
Recent reports have attempted to elaborate on the local interaction of tumor cells with the neuronal environment, where neurons, glial cells, and immune cells contribute to the formation of complex and dynamically heterogeneous glioma networks
.
Due to the loss of spatial organization information, single-cell analysis provides only indirect inference
of cellular interactions.
In the brain, spatial organization and function are closely related
.
Therefore, the researchers hypothesized that central nervous system malignancies were functionally and spatially organized
.
Spatially resolved transcriptomics is a new technique that enables in situ characterization of cellular interactions and tissues to decipher the ecosystem
of malignant brain tumors.
Given that scRNA-seq and spatial transcriptomics are not competitive but complementary, the integration of these two techniques is critical
.
In addition to spatially resolved transcriptomics, complementary molecular analysis is needed to fully understand the impact of
the microenvironment on tumor cells.
Cellular communication and metabolism are two key factors
that have a decisive influence on the dynamic adaptation of brain tumors, promoting growth, infiltration, and resistance to treatment.
Its metabolic alterations can be attributed to heterogeneity
in microenvironment regions in tumor metabolism.
For example, metabolic deterioration due to hypoxia significantly drives transcriptional adaptability and genomic instability; It also strengthens the interaction
between tumor cells and immune system cells.
A recent study demonstrated that epigenetic immune editing drives the acquired immune invasion program, leading to a landscape of spatial heterogeneity in glioblastoma; The need
to comprehensively understand the various transcriptional adaptations of gliomas induced by the microenvironment in the context of spatial resolution is further emphasized.
Study results
The researchers collected 28 tumor samples to draw spatially resolved transcriptomics maps, generating 88,793 different transcriptomes, age groups, and anatomical regions, and deciphering the transcriptional heterogeneity of spatial resolution.
The discovery of different transcriptional states in space is independent of cell cycle states, different transcriptional programs, and subclonal structures, and consistent with existing classification systems, confirming metabolic alterations
associated with reactive hypoxic procedures in GBM.
Exploring tumor-host interdependencies and environmental conditions in reactive immune regions contributes to understanding bidirectional isotype transitions
.
Conclusion of the study
The study elucidates the transcription program profile of the GBM region and maps the microenvironment landscape, including metabolism and tumor-host cell interactions
.
Researchers have demonstrated that the host environment plays an important role in remodeling genetic and transcriptional heterogeneity and the results of exploring patient heterogeneity, which provides new insights
into early GBM recurrence and resistance therapy.
The authors argue that tailored treatments need to be applied, emphasizing the importance of
personalized treatment in neuro-oncology.
