Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages

Glioblastoma is believed to originate from nervous system cells; however, a putative origin from vessel-associated progenitor cells has not been considered. We deeply single-cell RNA-sequenced glioblastoma progenitor cells of 18 patients and integrated 710 bulk tumors and 73,495 glioma single cells...

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Published in:Science advances 2022-06, Vol.8 (23), p.eabm6340-eabm6340
Main Authors: Hu, Yizhou, Jiang, Yiwen, Behnan, Jinan, Ribeiro, Mariana Messias, Kalantzi, Chrysoula, Zhang, Ming-Dong, Lou, Daohua, Häring, Martin, Sharma, Nilesh, Okawa, Satoshi, Del Sol, Antonio, Adameyko, Igor, Svensson, Mikael, Persson, Oscar, Ernfors, Patrik
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Computer Science
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container_issue 23
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container_title Science advances
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creator Hu, Yizhou
Jiang, Yiwen
Behnan, Jinan
Ribeiro, Mariana Messias
Kalantzi, Chrysoula
Zhang, Ming-Dong
Lou, Daohua
Häring, Martin
Sharma, Nilesh
Okawa, Satoshi
Del Sol, Antonio
Adameyko, Igor
Svensson, Mikael
Persson, Oscar
Ernfors, Patrik
description Glioblastoma is believed to originate from nervous system cells; however, a putative origin from vessel-associated progenitor cells has not been considered. We deeply single-cell RNA-sequenced glioblastoma progenitor cells of 18 patients and integrated 710 bulk tumors and 73,495 glioma single cells of 100 patients to determine the relation of glioblastoma cells to normal brain cell types. A novel neural network-based projection of the developmental trajectory of normal brain cells uncovered two principal cell-lineage features of glioblastoma, neural crest perivascular and radial glia, carrying defining methylation patterns and survival differences. Consistently, introducing tumorigenic alterations in naïve human brain perivascular cells resulted in brain tumors. Thus, our results suggest that glioblastoma can arise from the brains' vasculature, and patients with such glioblastoma have a significantly poorer outcome.
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subjects Biomedicine and Life Sciences
Cell Biology
Computer Science
SciAdv r-articles
title Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages
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