Development of an osteosarcoma model with MYCN amplification and TP53 mutation in hiPS cell‐derived neural crest cells Article Swipe
Kyosuke Mukae
,
Hisanori Takenobu
,
Yuki Endo
,
Masayuki Haruta
,
Tianyuan Shi
,
Shunpei Satoh
,
Miki Ohira
,
Michinori Funato
,
Junya Toguchida
,
Kenji Osafune
,
Tatsutoshi Nakahata
,
Hiroaki Kanda
,
Takehiko Kamijo
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1111/cas.15730
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1111/cas.15730
Mesenchymal stem cell‐ or osteoblast‐derived osteosarcoma is the most common malignant bone tumor. Its highly metastatic malignant phenotypes, which are often associated with a poor prognosis, have been correlated with the modulation of TP53‐ and cell‐cycle‐related pathways. MYC, which regulates the transcription of cell‐cycle modulating genes, is used as a representative prognostic marker for osteosarcoma. Another member of the MYC oncoprotein family, MYCN, is highly expressed in a subset of osteosarcoma, however its roles in osteosarcoma have not been fully elucidated. Here, we attempted to create an in vitro tumorigenesis model using hiPSC‐derived neural crest cells, which are precursors of mesenchymal stem cells, by overexpressing MYCN on a heterozygous TP53 hotspot mutation (c.733G>A; p.G245S) background. MYCN‐expressing TP53 mutated transformed clones were isolated by soft agar colony formation, and administered subcutaneously into the periadrenal adipose tissue of immunodeficient mice, resulting in the development of chondroblastic osteosarcoma. MYCN suppression decreased the proliferation of MYCN‐induced osteosarcoma cells, suggesting MYCN as a potential target for a subset of osteosarcoma treatment. Further, comprehensive analysis of gene expression and exome sequencing of MYCN‐induced clones indicated osteosarcoma‐specific molecular features, such as the activation of TGF‐β signaling and DNA copy number amplification of GLI1 . The model of MYCN‐expressing chondroblastic osteosarcoma was developed from hiPSC‐derived neural crest cells, providing a useful tool for the development of new tumor models using hiPSC‐derived progenitor cells with gene modifications and in vitro transformation.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/cas.15730
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cas.15730
- OA Status
- gold
- Cited By
- 8
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4317567517
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4317567517Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/cas.15730Digital Object Identifier
- Title
-
Development of an osteosarcoma model with MYCN amplification and TP53 mutation in hiPS cell‐derived neural crest cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-01-20Full publication date if available
- Authors
-
Kyosuke Mukae, Hisanori Takenobu, Yuki Endo, Masayuki Haruta, Tianyuan Shi, Shunpei Satoh, Miki Ohira, Michinori Funato, Junya Toguchida, Kenji Osafune, Tatsutoshi Nakahata, Hiroaki Kanda, Takehiko KamijoList of authors in order
- Landing page
-
https://doi.org/10.1111/cas.15730Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cas.15730Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cas.15730Direct OA link when available
- Concepts
-
Osteosarcoma, Cancer research, Biology, Neural crest, Mesenchymal stem cell, Carcinogenesis, Progenitor cell, Cell cycle, Stem cell, Pathology, Cell, Gene, Cell biology, Medicine, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 3, 2023: 2Per-year citation counts (last 5 years)
- References (count)
-
46Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.were | 121 |
| abstract_inverted_index.with | 23, 30, 226 |
| abstract_inverted_index.Here, | 82 |
| abstract_inverted_index.MYCN, | 63 |
| abstract_inverted_index.cells | 225 |
| abstract_inverted_index.crest | 95, 209 |
| abstract_inverted_index.exome | 174 |
| abstract_inverted_index.fully | 80 |
| abstract_inverted_index.mice, | 138 |
| abstract_inverted_index.model | 91, 199 |
| abstract_inverted_index.often | 21 |
| abstract_inverted_index.roles | 74 |
| abstract_inverted_index.tumor | 220 |
| abstract_inverted_index.using | 92, 222 |
| abstract_inverted_index.vitro | 89, 231 |
| abstract_inverted_index.which | 19, 39, 97 |
| abstract_inverted_index.cells, | 96, 103, 154, 210 |
| abstract_inverted_index.clones | 120, 178 |
| abstract_inverted_index.colony | 126 |
| abstract_inverted_index.common | 10 |
| abstract_inverted_index.create | 86 |
| abstract_inverted_index.genes, | 46 |
| abstract_inverted_index.highly | 15, 65 |
| abstract_inverted_index.marker | 53 |
| abstract_inverted_index.member | 57 |
| abstract_inverted_index.models | 221 |
| abstract_inverted_index.neural | 94, 208 |
| abstract_inverted_index.number | 193 |
| abstract_inverted_index.subset | 69, 163 |
| abstract_inverted_index.target | 160 |
| abstract_inverted_index.tissue | 135 |
| abstract_inverted_index.tumor. | 13 |
| abstract_inverted_index.useful | 213 |
| abstract_inverted_index.Another | 56 |
| abstract_inverted_index.TP53‐ | 34 |
| abstract_inverted_index.adipose | 134 |
| abstract_inverted_index.cell‐ | 3 |
| abstract_inverted_index.family, | 62 |
| abstract_inverted_index.hotspot | 111 |
| abstract_inverted_index.however | 72 |
| abstract_inverted_index.mutated | 118 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.Further, | 167 |
| abstract_inverted_index.TGF‐β | 188 |
| abstract_inverted_index.analysis | 169 |
| abstract_inverted_index.isolated | 122 |
| abstract_inverted_index.mutation | 112 |
| abstract_inverted_index.p.G245S) | 114 |
| abstract_inverted_index.attempted | 84 |
| abstract_inverted_index.decreased | 148 |
| abstract_inverted_index.developed | 205 |
| abstract_inverted_index.expressed | 66 |
| abstract_inverted_index.features, | 182 |
| abstract_inverted_index.indicated | 179 |
| abstract_inverted_index.malignant | 11, 17 |
| abstract_inverted_index.molecular | 181 |
| abstract_inverted_index.pathways. | 37 |
| abstract_inverted_index.potential | 159 |
| abstract_inverted_index.providing | 211 |
| abstract_inverted_index.regulates | 40 |
| abstract_inverted_index.resulting | 139 |
| abstract_inverted_index.signaling | 189 |
| abstract_inverted_index.activation | 186 |
| abstract_inverted_index.associated | 22 |
| abstract_inverted_index.correlated | 29 |
| abstract_inverted_index.expression | 172 |
| abstract_inverted_index.formation, | 127 |
| abstract_inverted_index.metastatic | 16 |
| abstract_inverted_index.modulating | 45 |
| abstract_inverted_index.modulation | 32 |
| abstract_inverted_index.precursors | 99 |
| abstract_inverted_index.progenitor | 224 |
| abstract_inverted_index.prognosis, | 26 |
| abstract_inverted_index.prognostic | 52 |
| abstract_inverted_index.sequencing | 175 |
| abstract_inverted_index.suggesting | 155 |
| abstract_inverted_index.treatment. | 166 |
| abstract_inverted_index.Mesenchymal | 1 |
| abstract_inverted_index.background. | 115 |
| abstract_inverted_index.development | 142, 217 |
| abstract_inverted_index.elucidated. | 81 |
| abstract_inverted_index.mesenchymal | 101 |
| abstract_inverted_index.oncoprotein | 61 |
| abstract_inverted_index.periadrenal | 133 |
| abstract_inverted_index.phenotypes, | 18 |
| abstract_inverted_index.suppression | 147 |
| abstract_inverted_index.transformed | 119 |
| abstract_inverted_index.administered | 129 |
| abstract_inverted_index.cell‐cycle | 44 |
| abstract_inverted_index.heterozygous | 109 |
| abstract_inverted_index.osteosarcoma | 6, 76, 153, 165, 203 |
| abstract_inverted_index.(c.733G>A; | 113 |
| abstract_inverted_index.amplification | 194 |
| abstract_inverted_index.comprehensive | 168 |
| abstract_inverted_index.modifications | 228 |
| abstract_inverted_index.osteosarcoma, | 71 |
| abstract_inverted_index.osteosarcoma. | 55, 145 |
| abstract_inverted_index.proliferation | 150 |
| abstract_inverted_index.transcription | 42 |
| abstract_inverted_index.tumorigenesis | 90 |
| abstract_inverted_index.MYCN‐induced | 152, 177 |
| abstract_inverted_index.chondroblastic | 144, 202 |
| abstract_inverted_index.overexpressing | 105 |
| abstract_inverted_index.representative | 51 |
| abstract_inverted_index.subcutaneously | 130 |
| abstract_inverted_index.hiPSC‐derived | 93, 207, 223 |
| abstract_inverted_index.immunodeficient | 137 |
| abstract_inverted_index.transformation. | 232 |
| abstract_inverted_index.MYCN‐expressing | 116, 201 |
| abstract_inverted_index.osteoblast‐derived | 5 |
| abstract_inverted_index.cell‐cycle‐related | 36 |
| abstract_inverted_index.osteosarcoma‐specific | 180 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5064427269 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| corresponding_institution_ids | https://openalex.org/I4210123465, https://openalex.org/I72253084 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5299999713897705 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.88708055 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |