# Single-cell genomic approaches to study the cellular origins of brain tumors

> **NIH NIH DP5** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $423,750

## Abstract

Summary Abstract
Brain tumors are responsible for an immense burden of disease due to their diversity, prevalence, poor
response to therapies, and high morbidity and mortality. More than half a million people in the United States
have a primary brain tumor or other central nervous system tumor, and about 80,000 new tumors are
diagnosed each year. However, the origins of brain tumors— i.e. the specific cell type from which each brain
tumor arises— remains enigmatic and is a fundamental unknown in our understanding of their biology. This
project will address this major gap by developing a novel single-cell genomics technology to identify the cells of
origin of brain tumors. Animal models have shown that the phenotype of the “cell of origin”— the first cell that
acquires the genetic mutations to initiate a tumor— often plays a major role in determining subsequent tumor
phenotype and behavior. The epigenetic legacy of the cell of origin is likely at play in human brain tumors as
well, but the identification of tumor cells of origin has not been possible due to a major technological
limitation— the absence of a method for systematically tracing lineages of cells in human tissues. We will
address this research challenge via three related aims: 1) Development of a novel single-cell technology called
TAPESTRY capable of reconstructing high-resolution lineage trees from human tissues for the first time.
TAPESTRY will achieve this by selectively capturing spontaneously occurring somatic mutations in tens of
thousands of single cells, while simultaneously profiling the transcriptomes of the same single cells, thereby
allowing reconstruction of phenotypically annotated lineage trees at feasible costs; 2) Application of
TAPESTRY to catalogue the hierarchy of progenitor cell lineages in normal cerebral cortex as a reference,
followed by identification of the cells of origin and early lineages of individual brain tumors within that hierarchy.
This aim will focus on three tumor types with likely different cells of origin: glioblastoma (the most common and
most lethal malignant brain tumor), anaplastic oligodendroglioma, and primitive neuroectodermal tumors; 3) In
situ spatial mapping of the early tumor lineages identified by TAPESTRY to understand whether they occupy
specific domains within tumors and whether they contribute to tumor migration and invasion. Overall, this work
will provide insight into a significant unknown factor in brain tumor etiology—the cell of origin—which, we
hypothesize plays a major and under-appreciated role in tumor biology. Identifying the cell of origin would
transform our understanding of why brain tumors arise where and when they do, their phenotypic diversity, and
importantly, could facilitate earlier detection, the creation of new animal models, and the design of lineage-
targeted therapies. Moreover, the technology developed here has the potential for major impact across cancer
biology and developmental biology research more gen...

## Key facts

- **NIH application ID:** 10216375
- **Project number:** 5DP5OD028158-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Gilad David Evrony
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2019-09-16 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216375

## Citation

> US National Institutes of Health, RePORTER application 10216375, Single-cell genomic approaches to study the cellular origins of brain tumors (5DP5OD028158-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216375. Licensed CC0.

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