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LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION

Publication ,  Conference
Regal, J; Guerra-Garcia, M; Jain, V; Chandramohan, V; Ashley, D; Gregory, S; Thompson, E; Lopez, G; Reitman, Z
Published in: Neuro-Oncology
June 12, 2023

Gangliogliomas are glioneuronal brain tumors that typically present in childhood or early adulthood. Though most often low-grade, new insights are needed to refine glioneuronal tumor classification and to identify therapeutic approaches, particularly for unresectable, high-grade, and/or recurrent disease. Gangliogliomas often possess a rare population of immature astrocyte-appearing CD34+ cells. CD34 is expressed in neuroectoderm neural precursor cells during embryogenesis. Neural cell CD34 expression is usually lost prior to birth. We hypothesized that CD34+ ganglioglioma cells represent tumor precursor/stem cells and closely resemble ganglioglioma cells of origin. To test this, we evaluated five gangliogliomas with single nucleus RNA-seq, cellular indexing of transcriptomes and epitopes by sequencing, and/or spatially-resolved RNA-seq. Developmental trajectory analyses uncovered a neoplastic cellular hierarchy, with CD34+PAX6+SOX2+MSI1+PECAM1-VWF-DCN-COL1A2- cells being the most primordial and precursor to neuron-like and macroglia-like neoplastic cell states. Gene regulatory network inference of CD34+ ganglioglioma cells indicated TCF7L2/MEIS1-PAX6 and SOX2-mediated transcriptional programming, similar to that found during neuroectodermal/neural development in utero. Spatially-resolved transcriptomics revealed a neuroectoderm neural precursor-like tumor cell niche relatively devoid of vascular and immune cells. We used these high-resolution results to deconvolute clinically-annotated transcriptomic data, confirming that CD34+ neural precursor-like cell-associated gene programs associate with gangliogliomas compared to other brain tumors. Together, these deep transcriptomic approaches characterized a ganglioglioma cellular hierarchy - identifying CD34+ neuroectoderm neural precursor-like tumor-initiating cells, corresponding regulatory transcriptional programs, cell signaling pathways, and associated immune cell states. These findings may facilitate improved ganglioglioma tumor classification, diagnosis, and therapeutic investigations.

Duke Scholars

Published In

Neuro-Oncology

DOI

EISSN

1523-5866

ISSN

1522-8517

Publication Date

June 12, 2023

Volume

25

Issue

Supplement_1

Start / End Page

i58 / i58

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1109 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
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Regal, J., Guerra-Garcia, M., Jain, V., Chandramohan, V., Ashley, D., Gregory, S., … Reitman, Z. (2023). LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION. In Neuro-Oncology (Vol. 25, pp. i58–i58). Oxford University Press (OUP). https://doi.org/10.1093/neuonc/noad073.223
Regal, Joshua, Maria Guerra-Garcia, Vaibhav Jain, Vidyalakshmi Chandramohan, David Ashley, Simon Gregory, Eric Thompson, Giselle Lopez, and Zachary Reitman. “LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION.” In Neuro-Oncology, 25:i58–i58. Oxford University Press (OUP), 2023. https://doi.org/10.1093/neuonc/noad073.223.
Regal J, Guerra-Garcia M, Jain V, Chandramohan V, Ashley D, Gregory S, et al. LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION. In: Neuro-Oncology. Oxford University Press (OUP); 2023. p. i58–i58.
Regal, Joshua, et al. “LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION.” Neuro-Oncology, vol. 25, no. Supplement_1, Oxford University Press (OUP), 2023, pp. i58–i58. Crossref, doi:10.1093/neuonc/noad073.223.
Regal J, Guerra-Garcia M, Jain V, Chandramohan V, Ashley D, Gregory S, Thompson E, Lopez G, Reitman Z. LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION. Neuro-Oncology. Oxford University Press (OUP); 2023. p. i58–i58.
Journal cover image

Published In

Neuro-Oncology

DOI

EISSN

1523-5866

ISSN

1522-8517

Publication Date

June 12, 2023

Volume

25

Issue

Supplement_1

Start / End Page

i58 / i58

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1109 Neurosciences