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<p>Pediatric low-grade gliomas (pLGGs) are the most common type of brain tumors in children, characterized by their typically slow growth and oncogene-induced senescence. Preclinical models provide the opportunity to investigate the effects of various treatments in a controlled setting before they are tested in human patients; however, reliable models for pLGGs are limited. Here we developed two organoid models for pLGGs, which, after engraftment into mice, exhibited low-grade features. Furthermore, the genome-wide DNA methylation and RNA profiles of the organoids demonstrated closer similarity to low-grade glioma entities compared to high-grade counterparts. Additionally, pLGG organoid-derived cells align with oligodendrocyte-like, astrocyte-like and MAPK signature clusters seen in patient tumors, indicating that the organoids generate a heterogeneous population of cancer cells, where cellular diversity may influence disease progression and treatment response.</p>

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Modeling pediatric low-grade glioma heterogeneity using human forebrain organoids

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月1日

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  • Gloria Leva,
  • Lucia Santomaso,
  • Matteo Gianesello,
  • Sara Patrizi,
  • Federica Ress,
  • Federico Cocchini,
  • Celeste Antonacci,
  • Francesca Gianno,
  • Luana Abballe,
  • Chiara Lago,
  • Noemi Pozza,
  • Gabriele Trentini,
  • Marina Cardano,
  • Simone Minasi,
  • Francesca Romana Buttarelli,
  • Manila Antonelli,
  • Davide Pernici,
  • Linda Petrucci,
  • Francesco Antonica,
  • Emma Busarello,
  • Martina Iannuzzi,
  • Alessia Soldano,
  • Toma Tebaldi,
  • Evelina Miele,
  • Elisabetta Ferretti,
  • Luca Tiberi

摘要

Pediatric low-grade gliomas (pLGGs) are the most common type of brain tumors in children, characterized by their typically slow growth and oncogene-induced senescence. Preclinical models provide the opportunity to investigate the effects of various treatments in a controlled setting before they are tested in human patients; however, reliable models for pLGGs are limited. Here we developed two organoid models for pLGGs, which, after engraftment into mice, exhibited low-grade features. Furthermore, the genome-wide DNA methylation and RNA profiles of the organoids demonstrated closer similarity to low-grade glioma entities compared to high-grade counterparts. Additionally, pLGG organoid-derived cells align with oligodendrocyte-like, astrocyte-like and MAPK signature clusters seen in patient tumors, indicating that the organoids generate a heterogeneous population of cancer cells, where cellular diversity may influence disease progression and treatment response.