RESUMO
Pediatric solid and central nervous system tumors are the leading cause of cancer-related death among children. Identifying new targeted therapies necessitates the use of pediatric cancer models that faithfully recapitulate the patient's disease. However, the generation and characterization of pediatric cancer models has significantly lagged behind adult cancers, underscoring the urgent need to develop pediatric-focused cell line resources. Herein, we establish a single-site collection of 261 cell lines, including 224 pediatric cell lines representing 18 distinct extracranial and brain childhood tumor types. We subjected 182 cell lines to multi-omics analyses (DNA sequencing, RNA sequencing, DNA methylation), and in parallel performed pharmacological and genetic CRISPR-Cas9 loss-of-function screens to identify pediatric-specific treatment opportunities and biomarkers. Our work provides insight into specific pathway vulnerabilities in molecularly defined pediatric tumor classes and uncovers biomarker-linked therapeutic opportunities of clinical relevance. Cell line data and resources are provided in an open access portal.
Assuntos
Neoplasias Encefálicas , Criança , Humanos , Neoplasias Encefálicas/patologia , Linhagem Celular TumoralRESUMO
The Genea016 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female Allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea016 was demonstrated with 77% of cells expressing Nanog, 95% Oct4, 53% Tra1-60 and 98% SSEA4, a PluriTest Pluripotency score of 28.4, Novelty score of 1.37 and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Técnicas de Cultura de Células/métodos , Linhagem Celular/citologia , Células-Tronco Embrionárias Humanas/citologia , Fosfatase Alcalina/metabolismo , Forma Celular , Hibridização Genômica Comparativa , DNA/metabolismo , Humanos , Cariotipagem , Reprodutibilidade dos Testes , Coloração e RotulagemRESUMO
The Genea057 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea057 was demonstrated with 97% of cells expressing Nanog, 81% Oct4, 75% Tra1-60 and 97% SSEA4, a PluriTest Pluripotency score of 27.59 and Novelty score of 1.32. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Técnicas de Cultura de Células/métodos , Linhagem Celular/citologia , Células-Tronco Embrionárias Humanas/citologia , Contagem de Células , Forma Celular , Hibridização Genômica Comparativa , Imunofluorescência , Humanos , Reprodutibilidade dos TestesRESUMO
The Genea043 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea043 was demonstrated with 92% of cells expressing Nanog, 95% Oct4, 61% Tra1-60 and 99% SSEA4, a PluriTest Pluripotency score of 31.74, Novelty score of 1.2 and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Células-Tronco Embrionárias Humanas/citologia , Fosfatase Alcalina/metabolismo , Blastocisto/citologia , Linhagem Celular , Sobrevivência Celular , Hibridização Genômica Comparativa , Genótipo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea002 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype by CGH and male Allele pattern through STR analysis. Pluripotency of Genea002 was demonstrated with 75% of cells expressing Nanog, 93% Oct4, 83% Tra1-60 and 98% SSEA4, a Pluritest pluripotency score of 24.55, Novelty score of 1.39, teratomas with tissues from all embryonic germ layers and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Células-Tronco Embrionárias Humanas/citologia , Fosfatase Alcalina/metabolismo , Blastocisto/citologia , Linhagem Celular , Sobrevivência Celular , Hibridização Genômica Comparativa , Genótipo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea042 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea042 was demonstrated with 81% of cells expressing Nanog, 95% Oct4, 53% Tra1-60 and 97% SSEA4, a PluriTest Pluripotency score of 30.06, Novelty score of 1.24 and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Microscopia de Fluorescência , Reação em Cadeia da Polimerase , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea052 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through CGH and STR analysis. Pluripotency of Genea052 was demonstrated with 85% of cells expressing Nanog, 87% Oct4, 60% Tra1-60 and 97% SSEA4, a PluriTest Pluripotency score of 27.21, Novelty score of 1.2 and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Alelos , Animais , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Cariótipo , Masculino , Camundongos , Microscopia de Fluorescência , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea047 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea047 was demonstrated with 88% of cells expressing Nanog, 95% Oct4, 59% Tra1-60 and 99% SSEA4, a PluriTest Pluripotency score of 30.86, Novelty score of 1.23 and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Alelos , Animais , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Cariótipo , Camundongos , Microscopia de Fluorescência , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea019 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype, female Allele pattern and unaffected Htt CAG repeat length, compared to HD affected sibling Genea020. Pluripotency of Genea019 was demonstrated with 75% of cells expressing Nanog, 89% Oct4, 48% Tra1-60 and 85% SSEA4, a Pluritest Pluripotency score of 22.97, Novelty score of 1.42, tri-lineage teratoma formation and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Alelos , Animais , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Cariótipo , Camundongos , Microscopia de Fluorescência , Teratoma/metabolismo , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea021 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analyses demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology, 71% of cells expressed Nanog, 84% Oct4, 23% Tra1-60 and 95% SSEA4, gave a Pluritest Pluripotency score of 21.85, Novelty of 1.42, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Síndrome de Down/patologia , Células-Tronco Embrionárias Humanas/citologia , Alelos , Animais , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Síndrome de Down/genética , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Cariótipo , Masculino , Camundongos , Microscopia de Fluorescência , Teratoma/metabolismo , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1.45, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Doença de Huntington/patologia , Animais , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Citometria de Fluxo , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Doença de Huntington/genética , Doença de Huntington/metabolismo , Cariótipo , Camundongos , Repetições de Microssatélites/genética , Microscopia de Fluorescência , Teratoma/metabolismo , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea078 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 76% of cells expressed Nanog, 93% Oct4, 67% Tra1-60 and 97% SSEA4 and gave a Pluritest Pluripotency score of 42.18, Novelty of 1.37. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Miopatias da Nemalina/patologia , Alelos , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Éxons , Feminino , Citometria de Fluxo , Heterozigoto , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Microscopia de Fluorescência , Proteínas Musculares/genética , Miopatias da Nemalina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Doença de Huntington/patologia , Alelos , Animais , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Citometria de Fluxo , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Cariótipo , Camundongos , Camundongos SCID , Repetições de Microssatélites/genética , Microscopia de Fluorescência , Teratoma/metabolismo , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea089 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 41 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a PluriTest Pluripotency score of 39.28, Novelty of 1.2. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Doença de Huntington/patologia , Alelos , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Citometria de Fluxo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Cariótipo , Repetições de Microssatélites/genética , Microscopia de Fluorescência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea067 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying expansion of CTG repeats in the DMPK gene, indicative of Myotonic Dystrophy Type 1 (DM1). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 97% Oct4, 73% Tra1-60 and 98% SSEA4 and gave a Pluritest Pluripotency score of 25.75, Novelty of 1.46. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Distrofia Miotônica/patologia , Alelos , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Citometria de Fluxo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Masculino , Repetições de Microssatélites/genética , Microscopia de Fluorescência , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Miotonina Proteína Quinase/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea079 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 86% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 98% SSEA4 and gave a PluriTest Pluripotency score of 30.25, Novelty of 1.21. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Miopatias da Nemalina/patologia , Alelos , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Éxons , Citometria de Fluxo , Deleção de Genes , Heterozigoto , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Masculino , Microscopia de Fluorescência , Proteínas Musculares/genética , Miopatias da Nemalina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea080 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 99% SSEA4 and gave a PluriTest Pluripotency score of 32.08, Novelty of 1.3. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Miopatias da Nemalina/patologia , Alelos , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Éxons , Citometria de Fluxo , Deleção de Genes , Heterozigoto , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Cariótipo , Masculino , Microscopia de Fluorescência , Proteínas Musculares/genética , Miopatias da Nemalina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Doença de Huntington/patologia , Alelos , Animais , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Citometria de Fluxo , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/transplante , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Cariótipo , Camundongos , Repetições de Microssatélites/genética , Microscopia de Fluorescência , Teratoma/metabolismo , Teratoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
The Genea091 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 98% SSEA4 and gave a Pluritest pluripotency score of 38.36, Novelty of 1.35. The cell line was negative for Mycoplasma and visible contamination.
Assuntos
Blastocisto/citologia , Células-Tronco Embrionárias Humanas/citologia , Doença de Huntington/patologia , Alelos , Células Cultivadas , Reprogramação Celular , Hibridização Genômica Comparativa , Feminino , Citometria de Fluxo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Cariótipo , Repetições de Microssatélites/genética , Microscopia de Fluorescência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The Genea023 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through CGH and STR analysis. Pluripotency of Genea023 was demonstrated with 85% of cells expressed Nanog, 98% Oct4, 55% Tra1-60 and 98% SSEA4, gave a Pluritest Pluripotency score of 42.76, Novelty of 1.23, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.
