BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas
- Childhood Cancer & Cell Death (C3) team, LabEx DEVweCAN, Institut Convergence Plascan, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, France
- University of Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Centre Oscar Lambret, France
- Université Paris Cité, CNRS, Institut Jacques Monod, France
- Multisite Institute of Pathology, Groupement Hospitalier Est du CHU de Lyon, Hôpital Femme-Mère Enfant, France
- Platform of Cancer Genomics, Centre Léon Bérard, France
- Preclinical Therapeutics and Drug Delivery Research Program, Department of Oncology, Hospital Sant Joan de Déu, Spain
- Centre de Recherche en Cancérologie de Marseille (CRCM), Université Aix-Marseille, Institut Paoli- Calmettes, Centre de Lutte Contre le Cancer de la région PACA, INSERM 1068, CNRS 7258, France
- Department of Pediatric Oncology, Institute of Pediatric Hematology and Oncology (IHOPe), Centre Léon Bérard, France
- GLIMMER Of lIght (GLIoblastoma MetabolisM, HetERogeneity, and OrganoIds) team, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, France
Figures
Figure 1 with 1 supplement
Bone morphogenetic protein (BMP) pathway activation coincides with high BMP2/7 levels in ACVR1 WT-H3.3K27M pDMG.
(A) Principal component analysis (PCA) of ACVR1 WT (red) and mutant pediatric diffuse midline gliomas (pDMG) (blue) samples based on transcriptomic data from cohort 1. (B) Heatmap representing the …
Figure 1—figure supplement 1
Bone morphogenetic protein (BMP) pathway activation coincides with high BMP2/7 levels in ACVR1 WT-H3.3K27M pDMG.
(A) Principal component analysis (PCA) of ACVR1 WT (red) and mutant pediatric diffuse midline gliomas (pDMG) (blue) samples based on transcriptomic data from cohort 2. (B) Heatmap representing the …
Figure 2 with 1 supplement
BMP7 induces a specific transcriptomic and phenotypic switch in a H3.3K27M mutant glioma context.
(A) BMP7 (left) and BMP2 (right) expressions in H3.3WT (green) versus H3.3K27M (purple) SF188 and Res259 cells. Gene expressions were analyzed by qRT-PCR relative to HPRT1 expression. Means ± std …
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Figure 2—source data 1
Uncropped and labeled gels for Figure 2.
- https://cdn.elifesciences.org/articles/91313/elife-91313-fig2-data1-v1.zip
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Figure 2—source data 2
Raw unedited gels for Figure 2.
- https://cdn.elifesciences.org/articles/91313/elife-91313-fig2-data2-v1.zip
Figure 2—figure supplement 1
H3.3K27M mutant context potentiates BMP7-induced transcriptomic and phenotypic switch in a glioma model.
(A) BMP2, BMP7, and BMP4 normalized expression from transcriptomic data of Res259-H3.3WT (green) versus Res259-H3.3K27M (purple). Means ± std are represented (n=3). (B) BMP4 expression between …
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Figure 2—figure supplement 1—source data 1
Uncropped and labeled gels for Figure 2—figure supplement 1.
- https://cdn.elifesciences.org/articles/91313/elife-91313-fig2-figsupp1-data1-v1.zip
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Figure 2—figure supplement 1—source data 2
Raw unedited gels for Figure 2—figure supplement 1.
- https://cdn.elifesciences.org/articles/91313/elife-91313-fig2-figsupp1-data2-v1.zip
Figure 3 with 1 supplement
Combined tumor-autonomous BMP2/BMP7 expression drives a quiescent-invasive tumor cell state in pediatric diffuse midline gliomas (pDMG).
(A) BMP2 expression after hypoxia or ONC201 treatment. Gene expression was analyzed by QRT-PCR relative to HPRT1 expression. Means ± std are represented (n=3). *p<0.05. (B) Growth monitoring of …
Figure 3—figure supplement 1
Combined tumor-autonomous BMP2/BMP7 expression drives a quiescent-invasive tumor cell state in pediatric diffuse midline gliomas (pDMG).
(A) Bone morphogenetic protein (BMP) ligands expression analyzed by qRT-PCR relative to five housekeeping genes levels in three different Diffuse Intrinsic Pontine Gliomas (DIPG) cell lines. …
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Figure 3—figure supplement 1—source data 1
Uncropped and labeled gels for Figure 3—figure supplement 1.
- https://cdn.elifesciences.org/articles/91313/elife-91313-fig3-figsupp1-data1-v1.zip
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Figure 3—figure supplement 1—source data 2
Raw unedited gels for Figure 3—figure supplement 1.
- https://cdn.elifesciences.org/articles/91313/elife-91313-fig3-figsupp1-data2-v1.zip
Additional files
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Supplementary file 1
Analysis of the profile of expression of BMP pathway in pDMG.
(a) List of the BMP target genes used for the heatmaps shown in Figure 1B and Figure 1—figure supplement 1B. (b) Average BMP ligand expression (natural log) per sample in the spatial transcriptomic dataset of DMG samples. (c) Normalized expression matrix (vst) of BMP pathway genes from cohort 3, including those shown in Figure 1—figure supplement 1E. (d) Histone mutation of samples from cohort 3.
- https://cdn.elifesciences.org/articles/91313/elife-91313-supp1-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/91313/elife-91313-mdarchecklist1-v1.pdf
