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"https://publications-affiliated.scilifelab.se/researcher/6ae643d4831f469c95c3d5b3955784ea.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}], "type": "posted-content", "published": "2023-03-31", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1158/0008-5472.c.6514337", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:10:28.433Z", "modified": "2026-08-20T12:10:29.634Z"}, {"entity": "publication", "iuid": "065e2ce2ee5b4c6bb5662444e9866769", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/065e2ce2ee5b4c6bb5662444e9866769.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/065e2ce2ee5b4c6bb5662444e9866769"}}, "title": "Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.", "authors": [{"family": "Borgenvik", "given": "Anna", "initials": "A", "orcid": "0000-0003-4696-7703", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca3b4c4e7b2b4fe4867c4e356957d4c9.json"}}, {"family": "Holmberg", "given": "Karl O", "initials": "KO", "orcid": "0000-0002-4402-0586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/469c34ade5f34855880bd40a0ed93a5b.json"}}, {"family": "Bolin", "given": "Sara", "initials": "S", "orcid": "0000-0003-2835-1518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/144233601c624bcd815822ff601d5e3e.json"}}, {"family": "Zhao", "given": "Miao", "initials": "M", "orcid": "0000-0002-4895-1177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/75b5d6dc5cde46b8aca859fb961bf1de.json"}}, {"family": "Savov", "given": "Vasil", "initials": "V", "orcid": "0000-0003-2347-1975", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e70244e16a3478e83abd7072ec7610b.json"}}, {"family": "Ros\u00e9n", "given": "Gabriela", "initials": "G", "orcid": "0000-0002-7762-1468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4bd52a448ba4dae883c2e14cddd2699.json"}}, {"family": "Hutter", "given": "Sonja", "initials": "S", "orcid": "0000-0003-3340-9315", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/68742a90cc194135a0eb33d52fe8b17a.json"}}, {"family": "Garancher", "given": "Alexandra", "initials": "A", "orcid": "0000-0001-5779-2860", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a08bf535ab73447baf9f6fef6a2a34cd.json"}}, {"family": "Rahmanto", "given": "Aldwin Suryo", "initials": "AS", "orcid": "0000-0002-4593-286X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/59328511ffe441f08443f83089cc909b.json"}}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4557-2390", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad8f5ab0560d4b7596ddd5e407b96d8f.json"}}, {"family": "Olsen", "given": "Thale Kristin", "initials": "TK", "orcid": "0000-0003-4655-7384", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/edb08108179a4b94a69eeca5809df636.json"}}, {"family": "Mainwaring", "given": "Oliver J", "initials": "OJ", "orcid": "0000-0002-7973-9849", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29515b9bedc74325aa50a0da62cd299a.json"}}, {"family": "Sattanino", "given": "Damiana", "initials": "D", "orcid": "0000-0002-2747-4842", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e621b0c6b77443f083541dd2fd65ab34.json"}}, {"family": "Verbaan", "given": "Annemieke D", "initials": "AD", "orcid": "0000-0001-6793-0577", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/625389e761a746d6b9c65ab0c81d8582.json"}}, {"family": "Rusert", "given": "Jessica M", "initials": "JM", "orcid": "0000-0003-0751-2693", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19ba859c845b4578b0b7fe729033c01a.json"}}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3942-6271", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63e6602d2807417684239b93eb065a26.json"}}, {"family": "Bravo", "given": "Mar Ballester", "initials": "MB", "orcid": "0000-0002-1371-6679", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4fc8169b243f403bbb9d85a2cc51a20a.json"}}, {"family": "Dang", "given": "Yonglong", "initials": "Y", "orcid": "0000-0001-9705-5507", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a828f29d1e8f40a69087ea74c89bc32c.json"}}, {"family": "Wenz", "given": "Amelie S", "initials": "AS", "orcid": "0000-0003-1929-382X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/262d770d769340bc8cf743701280a879.json"}}, {"family": "Richardson", "given": "Stacey", "initials": "S", "orcid": "0000-0003-1841-6330", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bae77ca73b1845cb94fbae185a0d5d72.json"}}, {"family": "Fotaki", "given": "Grammatiki", "initials": "G", "orcid": "0000-0002-1343-1921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b70b2fd7c1e348668fb7355bec1fcc3b.json"}}, {"family": "Hill", "given": "Rebecca M", "initials": "RM", "orcid": "0000-0001-8405-2219", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1259bdc29b04296a844a8e51c538990.json"}}, {"family": "Dubuc", "given": "Adrian M", "initials": "AM", "orcid": "0000-0002-3447-6715", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/98d65b7575504dd7bc1419885b7c5bdd.json"}}, {"family": "Kalushkova", "given": "Antonia", "initials": "A", "orcid": "0000-0003-4535-506X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d630aa01038d4be68a001ae0fd4f3def.json"}}, {"family": "Remke", "given": "Marc", "initials": "M", "orcid": "0000-0002-9404-9993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/975d2595635e45c49b84050b802a9251.json"}}, {"family": "\u010can\u010der", "given": "Matko", "initials": "M", "orcid": "0000-0001-5825-5151", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05cbffef1ba74a4890860f33af1f5719.json"}}, {"family": "Jernberg-Wiklund", "given": "Helena", "initials": "H", "orcid": "0000-0002-9319-7986", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c1e229ba71ec4129ac7ca516f90838ef.json"}}, {"family": "Giraud", "given": "G\u00e9raldine", "initials": "G", "orcid": "0000-0002-2771-9889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b71981055bfa4c1180c753e61b5b0919.json"}}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ffb9d3c94e54fac97be6c78586940eb.json"}}, {"family": "Taylor", "given": "Michael D", "initials": "MD", "orcid": "0000-0001-7009-3466", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/619748747921467fa6c6ec4a973f2d1d.json"}}, {"family": "Sangfelt", "given": "Olle", "initials": "O", "orcid": "0000-0002-0316-0195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2bc4930422a046f69295e2c59a569657.json"}}, {"family": "Clifford", "given": "Steven C", "initials": "SC", "orcid": "0000-0003-4893-2184", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd7e72eebce545f99f8d96a4ead4b395.json"}}, {"family": "Sch\u00fcller", "given": "Ulrich", "initials": "U", "orcid": "0000-0002-8731-1121", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6bfed174354240068d313e96bc371611.json"}}, {"family": "Wechsler-Reya", "given": "Robert J", "initials": "RJ", "orcid": "0000-0002-7463-8352", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36ca40f1c54d43d0af707c509bff1e9a.json"}}, {"family": "Weishaupt", "given": "Holger", "initials": "H", "orcid": "0000-0002-0364-2709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ae643d4831f469c95c3d5b3955784ea.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}], "type": "journal article", "published": "2022-12-16", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "82", "issue": "24", "pages": "4586-4603", "issn-l": "0008-5472"}, "abstract": "Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.\n\nSOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.", "doi": "10.1158/0008-5472.CAN-22-2108", "pmid": "36219398", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9755969"}, {"db": "pii", "key": "709709"}], "notes": [], "created": "2026-08-20T12:11:07.388Z", "modified": "2026-08-20T12:11:07.663Z"}, {"entity": "publication", "iuid": "9dcdc4592a8c4e0dab74f807fc254b1b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9dcdc4592a8c4e0dab74f807fc254b1b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9dcdc4592a8c4e0dab74f807fc254b1b"}}, "title": "SOX9 Defines Distinct Populations of Cells in SHH Medulloblastoma but Is Not Required for Math1-Driven Tumor Formation.", "authors": [{"family": "Adolphe", "given": "Christelle", "initials": "C"}, {"family": "Millar", "given": "Amanda", "initials": "A"}, {"family": "Kojic", "given": "Marija", "initials": "M", "orcid": "0000-0001-6437-283X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77e8f76b0a144796becbc1dab6da9205.json"}}, {"family": "Barkauskas", "given": "Deborah S", "initials": "DS"}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3942-6271", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63e6602d2807417684239b93eb065a26.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}, {"family": "Hediyeh-Zadeh", "given": "Soroor", "initials": "S", "orcid": "0000-0001-7513-6779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5a9996c51c9d43c6a40db9c46d213399.json"}}, {"family": "Tan", "given": "Chin Wee", "initials": "CW", "orcid": "0000-0001-9695-7218", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5277887d70f84d1d98fa163ee066817a.json"}}, {"family": "Davis", "given": "Melissa J", "initials": "MJ", "orcid": "0000-0003-4864-7033", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca0ff39b0e06406d9bf637043b2e2221.json"}}, {"family": "Genovesi", "given": "Laura A", "initials": "LA", "orcid": "0000-0001-6277-8422", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35c473636ad549d5a005b2680901551c.json"}}, {"family": "Wainwright", "given": "Brandon J", "initials": "BJ"}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "Mol. Cancer Res.", "issn": "1557-3125", "volume": "19", "issue": "11", "pages": "1831-1839", "issn-l": "1541-7786"}, "abstract": "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 SOX9low GCP-like tumor cells constitute the bulk of both infant (Math1Cre:Ptch1 ) and adult (lox/loxPtch1 ) SHH-MB mouse models. Human medulloblastoma single-cell RNA data analyses reveal three distinct LacZ/+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 ) revealed no overt phenotype and loss of lox/loxSox9 in SHH-MB (Math1Cre:Ptch1 ) does not affect tumor formation. IMPLICATIONS: Despite preclinical data indicating SOX9 plays a key role in SHH-MB biology, our data argue against SOX9 as a viable therapeutic target.lox/lox;Sox9lox/lox", "doi": "10.1158/1541-7786.MCR-21-0117", "pmid": "34330843", "labels": [], "xrefs": [{"db": "pii", "key": "1541-7786.MCR-21-0117"}], "notes": [], "created": "2026-08-20T12:14:25.096Z", "modified": "2026-08-20T12:14:25.210Z"}, {"entity": "publication", "iuid": "8fe4a1d767fc4ad7bc41eb58710cc1bd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8fe4a1d767fc4ad7bc41eb58710cc1bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8fe4a1d767fc4ad7bc41eb58710cc1bd"}}, "title": "Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells.", "authors": [{"family": "Susanto", "given": "Evelyn", "initials": "E"}, {"family": "Marin Navarro", "given": "Ana", "initials": "A"}, {"family": "Zhou", "given": "Leilei", "initials": "L"}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3942-6271", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63e6602d2807417684239b93eb065a26.json"}}, {"family": "van Bree", "given": "Niek", "initials": "N", "orcid": "0000-0001-5010-3524", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afdb3d47b0be46cbbf7e10f7367f6d7b.json"}}, {"family": "Stantic", "given": "Marina", "initials": "M"}, {"family": "Moslem", "given": "Mohsen", "initials": "M", "orcid": "0000-0002-2440-9586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac548b831c044a53ac324691083df9e1.json"}}, {"family": "Tailor", "given": "Jignesh", "initials": "J"}, {"family": "Rietdijk", "given": "Jonne", "initials": "J"}, {"family": "Zubillaga", "given": "Veronica", "initials": "V", "orcid": "0000-0002-8806-939X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0feb462e3293492bae0e051990b387df.json"}}, {"family": "H\u00fcbner", "given": "Jens-Martin", "initials": "JM"}, {"family": "Weishaupt", "given": "Holger", "initials": "H"}, {"family": "Wolfsberger", "given": "Johanna", "initials": "J"}, {"family": "Alafuzoff", "given": "Irina", "initials": "I", "orcid": "0000-0002-6249-569X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0d5a2e976bc84739a957f2b12517df7e.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Magnaldo", "given": "Thierry", "initials": "T", "orcid": "0000-0001-9174-8599", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/09542eee2b7748769298e9d4fcdc5a22.json"}}, {"family": "Siesj\u00f6", "given": "Peter", "initials": "P"}, {"family": "Johnsen", "given": "John Inge", "initials": "JI", "orcid": "0000-0003-1277-812X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e63aa6bb0fba481abeb58c2f1568b3c9.json"}}, {"family": "Kool", "given": "Marcel", "initials": "M", "orcid": "0000-0002-6557-5468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/da81ade40cfb45329b5ef3a190834913.json"}}, {"family": "Tammimies", "given": "Kristiina", "initials": "K", "orcid": "0000-0002-8324-4697", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/480cdbabfc57460f967e6921f12e6ec4.json"}}, {"family": "Darabi", "given": "Anna", "initials": "A", "orcid": "0000-0003-4326-8149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb9f19a0c8694ee79ca515a79976d146.json"}}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}, {"family": "Falk", "given": "Anna", "initials": "A", "orcid": "0000-0003-1634-8610", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a8825c33511418a83eceffdb530dadb.json"}}, {"family": "Wilhelm", "given": "Margareta", "initials": "M", "orcid": "0000-0002-0516-9724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b22feedd1d3c464ba7d8f6635fb00826.json"}}], "type": "journal article", "published": "2020-08-18", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "33", "pages": "20127-20138", "issn-l": "0027-8424"}, "abstract": "Medulloblastoma is the most common malignant brain tumor in children. Here we describe a medulloblastoma model using Induced pluripotent stem (iPS) cell-derived human neuroepithelial stem (NES) cells generated from a Gorlin syndrome patient carrying a germline mutation in the sonic hedgehog (SHH) receptor PTCH1. We found that Gorlin NES cells formed tumors in mouse cerebellum mimicking human medulloblastoma. Retransplantation of tumor-isolated NES (tNES) cells resulted in accelerated tumor formation, cells with reduced growth factor dependency, enhanced neurosphere formation in vitro, and increased sensitivity to Vismodegib. Using our model, we identified LGALS1 to be a GLI target gene that is up-regulated in both Gorlin tNES cells and SHH-subgroup of medulloblastoma patients. Taken together, we demonstrate that NES cells derived from Gorlin patients can be used as a resource to model medulloblastoma initiation and progression and to identify putative targets.", "doi": "10.1073/pnas.1920521117", "pmid": "32747535", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7443968"}, {"db": "pii", "key": "1920521117"}], "notes": [], "created": "2026-08-20T09:30:35.661Z", "modified": "2026-08-20T09:30:36.075Z"}]}