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SOX9 Defines Distin...
SOX9 Defines Distinct Populations of Cells in SHH Medulloblastoma but Is Not Required for Math1-Driven Tumor Formation
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- Adolphe, Christelle (författare)
- Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia.
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- Millar, Amanda (författare)
- Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia.
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- Kojic, Marija (författare)
- Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia.
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- Barkauskas, Deborah S. (författare)
- Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
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- Sundström, Anders (författare)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Swartling, Fredrik J., 1975- (författare)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Hediyeh-Zadeh, Soroor (författare)
- Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Med Biol, Melbourne, Vic, Australia.
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- Tan, Chin Wee (författare)
- Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Med Biol, Melbourne, Vic, Australia.
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- Davis, Melissa J. (författare)
- Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Med Biol, Melbourne, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Clin Pathol, Melbourne, Vic, Australia.
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- Genovesi, Laura A. (författare)
- Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia.
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- Wainwright, Brandon J. (författare)
- Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia.
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Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. (creator_code:org_t)
- American Association For Cancer Research (AACR), 2021
- 2021
- Engelska.
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Ingår i: Molecular Cancer Research. - : American Association For Cancer Research (AACR). - 1541-7786 .- 1557-3125. ; 19:11, s. 1831-1839
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Medulloblastoma is the most common malignant pediatric brain tumor and there is an urgent need for molecularly targeted and subgroup-specific therapies. The stem cell factor SOX9, has been proposed as a potential therapeutic target for the treatment of Sonic Hedgehog medulloblastoma (SHH-MB) subgroup tumors, given its role as a downstream target of Hedgehog signaling and in functionally promoting SHH-MB metastasis and treatment resistance. However, the functional requirement for SOX9 in the genesis of medulloblastoma remains to be determined. Here we report a previously undocumented level of SOX9 expression exclusively in proliferating granule cell precursors ( GCP) of the postnatal mouse cerebellum, which function as the medulloblastoma-initiating cells of SHH-MBs. Wild-type GCPs express comparatively lower levels of SOX9 than neural stem cells and mature astroglia and SOX9(low) GCP-like tumor cells constitute the bulk of both infant (Math1Cre: Ptch1(lox/lox)) and adult (Ptch1(LacZ/+)) SHH-MB mouse models. Human medulloblastoma single-cell RNA data analyses reveal three distinct SOX9 populations present in SHH-MB and noticeably absent in other medulloblastoma subgroups: SOX9(+)MATH1(+) (GCP), SOX9(+)GFAP(+) (astrocytes) and SOX9(+)MATH1(+)GFAP(+) (potential tumor-derived astrocytes). To functionally address whether SOX9 is required as a downstream effector of Hedgehog signaling in medulloblastoma tumor cells, we ablated Sox9 using a Math1Cre model system. Surprisingly, targeted ablation of Sox9 in GCPs (Math1Cre:Sox9(lox/lox)) revealed no overt phenotype and loss of Sox9 in SHH-MB (Math1Cre:Ptch1(lox/lox);Sox9(lox/lox)) does not affect tumor formation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Adolphe, Christe ...
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Millar, Amanda
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Kojic, Marija
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Barkauskas, Debo ...
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Sundström, Ander ...
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Swartling, Fredr ...
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Hediyeh-Zadeh, S ...
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Tan, Chin Wee
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Davis, Melissa J ...
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Genovesi, Laura ...
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Wainwright, Bran ...
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Uppsala universitet