Scientific pre-print featuring
customer-generated data demonstrates the power of single cell
spatial analysis to more directly assess unique tissue
microenvironments and cell-cell interactions
PLEASANTON, Calif., Oct. 26,
2023 /PRNewswire/ -- 10x Genomics, Inc.
(Nasdaq: TXG), a leader in single cell and spatial biology,
announced today that the 10x Xenium Analyzer was used in a study
recently published on bioRxiv characterizing
radiation-resistance mechanisms of diffuse midline gliomas (DMGs).
Led by researchers at Duke University,
the study also provides a lens by which to understand clinical
response in patients for current and future clinical trials using a
novel kinase inhibitor as part of DMG therapeutic strategies.
The study, "Ataxia-telangiectasia mutated (Atm)
disruption sensitizes spatially-directed H3.3K27M/TP53 diffuse
midline gliomas to radiation therapy," is among the first
scientific preprints to include customer-generated data using the
Xenium In Situ platform from 10x Genomics. The high-plex,
high-resolution single cell spatial mapping of Xenium was behind
many critical conclusions in this study, including revealing key
transcriptomic changes, the role of specific tumor compartments,
key cell communication pathways and the mechanisms by which key
genes function within the therapeutic response.
Researchers conducting the study analyzed formalin-fixed
paraffin-embedded tissue sections of a mouse brain tumor model that
mimics the common human DMG genetic drivers and to examine the
molecular and cellular mechanisms driving radiation efficacy or
resistance in these tumors. The study put particular focus on the
role that loss of Atm, which encodes a protein responsible
for cellular response to double-stranded DNA damage, plays in
treatment response.
"The single cell resolution enabled us to advance beyond
deductive science," said Dr. Simon
Gregory, co-senior author and Professor and Director of the
Brain Tumor Omics Program in the Duke
University Department of Neurosurgery and Director of the
Molecular Genomics Core at the Duke Molecular Physiology Institute.
"We were able to delve into the cellular composition of unique
tumor compartments and quantify the spatial proximity between key
cell types, revealing how the spatial relationship between tumor
and immune cells changed in response to a new therapeutic
intervention."
Dr. Zach Reitman, lead author and Assistant Professor of
Radiation Oncology, Pathology and Neurosurgery, said, "These are
diffuse tumors that infiltrate the normal brain. We wondered how
malignant cells within the tumor would respond to treatments
compared to those in the infiltrating edge. We were able to tease
apart how specific cell types in specific locations, such as the
tumor core and infiltrating edge, responded to different
treatments. This approach could help us understand mechanisms of
treatment efficacy, which will help us design future clinical
trials and come up with combination therapies to overcome treatment
resistance."
Ben Hindson, Co-founder and Chief Scientific Officer at 10x
Genomics, said, "This is a powerful, groundbreaking discovery. It
is awesome to see our customers using Xenium in their own labs with
such an incredible and immediate impact. We look forward to seeing
how researchers around the world continue to use 10x products to
fuel discoveries that push our understanding of health and disease
forward."
The authors began by generating several DMG mouse models
and identifying the conditions under which Atm loss or
pharmacological inhibition with brain-penetrant ATM inhibitor
AZD1390 leads tumors to exhibit increased sensitivity to radiation.
After these genetic experiments implicated tumor suppressor p53
loss as the principal driver of Atm loss–mediated
sensitivity to radiation, the researchers used the pre-designed
Xenium Mouse Brain Gene Expression Panel to profile key cell types
in the brain and designed a Custom Add-on Panel to examine
DMG-specific markers. The combination of the pre-designed and
custom panels allowed researchers to profile compartment-specific
gene expression changes of 298 targets at single cell
resolution.
Irradiation treatment was observed to cause differential
expression in cell cycle regulators and cell-fate-regulating
transcription factors, while the combination of irradiation
and Atm loss also impacted Semaphorin genes, which have
been previously implicated in glioma proliferation and expansion.
The researchers next estimated the distances between tumor cells
and other cell types revealing neoplastic tumor cells could be
found in closer proximity to certain immune cells as a result of
Atm loss or irradiation, but this effect was most pronounced
in Atm-null irradiated brains.
Additional analyses of the Xenium data revealed a complex
interplay between p21 status, a downstream target of p53, and
Atm-mediated radiosensitivity, leading the authors to
emphasize the importance of considering an animal model's or
patient's p21 status for clinical trials involving ATM
inhibitors.
To learn more about this study, read the full article.
About 10x Genomics
10x Genomics is a life science technology company building
products to accelerate the mastery of biology and advance human
health. Our integrated solutions include instruments, consumables
and software for single cell and spatial biology, which help
academic and translational researchers and biopharmaceutical
companies understand biological systems at a resolution and scale
that matches the complexity of biology. Our products are behind
breakthroughs in oncology, immunology, neuroscience and more,
fueling powerful discoveries that are transforming the world's
understanding of health and disease. To learn more, visit
10xgenomics.com or connect with us on LinkedIn or X (Twitter).
Contacts
Investors: investors@10xgenomics.com
Media: media@10xgenomics.com
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SOURCE 10x Genomics, Inc