RESUMEN
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.
Asunto(s)
Neoplasias Encefálicas , Niño , Humanos , Neoplasias Encefálicas/patología , Línea Celular TumoralRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Células Madre Embrionarias Humanas/metabolismo , Humanos , Cariotipo , Microscopía Fluorescente , Reacción en Cadena de la Polimerasa , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Alelos , Animales , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Cariotipo , Masculino , Ratones , Microscopía Fluorescente , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Alelos , Animales , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Cariotipo , Ratones , Microscopía Fluorescente , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Alelos , Animales , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Cariotipo , Ratones , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Síndrome de Down/patología , Células Madre Embrionarias Humanas/citología , Alelos , Animales , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Síndrome de Down/genética , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Cariotipo , Masculino , Ratones , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Enfermedad de Huntington/patología , Animales , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Citometría de Flujo , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Cariotipo , Ratones , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Miopatías Nemalínicas/patología , Alelos , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Exones , Femenino , Citometría de Flujo , Heterocigoto , Células Madre Embrionarias Humanas/metabolismo , Humanos , Cariotipo , Microscopía Fluorescente , Proteínas Musculares/genética , Miopatías Nemalínicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Enfermedad de Huntington/patología , Alelos , Animales , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Citometría de Flujo , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Cariotipo , Ratones , Ratones SCID , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Enfermedad de Huntington/patología , Alelos , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Citometría de Flujo , Células Madre Embrionarias Humanas/metabolismo , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Cariotipo , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Distrofia Miotónica/patología , Alelos , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Citometría de Flujo , Células Madre Embrionarias Humanas/metabolismo , Humanos , Cariotipo , Masculino , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Distrofia Miotónica/genética , Distrofia Miotónica/metabolismo , Proteína Quinasa de Distrofia Miotónica/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Miopatías Nemalínicas/patología , Alelos , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Exones , Citometría de Flujo , Eliminación de Gen , Heterocigoto , Células Madre Embrionarias Humanas/metabolismo , Humanos , Cariotipo , Masculino , Microscopía Fluorescente , Proteínas Musculares/genética , Miopatías Nemalínicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Miopatías Nemalínicas/patología , Alelos , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Exones , Citometría de Flujo , Eliminación de Gen , Heterocigoto , Células Madre Embrionarias Humanas/metabolismo , Humanos , Cariotipo , Masculino , Microscopía Fluorescente , Proteínas Musculares/genética , Miopatías Nemalínicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Enfermedad de Huntington/patología , Alelos , Animales , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Citometría de Flujo , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Cariotipo , Ratones , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Enfermedad de Huntington/patología , Alelos , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Citometría de Flujo , Células Madre Embrionarias Humanas/metabolismo , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Cariotipo , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
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.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Animales , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Cuerpos Embrioides/citología , Cuerpos Embrioides/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Cariotipo , Masculino , Ratones , Microscopía Fluorescente , Reacción en Cadena de la Polimerasa , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
The Genea049 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. 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, 90% of cells expressed Nanog, 96% Oct4, 80% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 23.16, Novelty of 1.43 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.
Asunto(s)
Células Madre Embrionarias Humanas/citología , Línea Celular , Reprogramación Celular , Hibridación Genómica Comparativa , Femenino , Eliminación de Gen , Células Madre Embrionarias Humanas/metabolismo , Humanos , Cariotipo , Proteínas de Microfilamentos , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Distrofias Musculares/metabolismo , Distrofias Musculares/patología , Proteínas Nucleares/genética , Proteínas de Unión al ARN , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The Genea022 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 Genea022 was demonstrated with 84% of cells expressed Nanog, 98% Oct4, 55% Tra1-60 and 97% SSEA4, gave a Pluritest Pluripotency score of 42.95, Novelty of 1.23, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.
Asunto(s)
Blastocisto/citología , Células Madre Embrionarias Humanas/citología , Alelos , Animales , Células Cultivadas , Reprogramación Celular , Hibridación Genómica Comparativa , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Cariotipo , Masculino , Ratones , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
The Genea017 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, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.
Asunto(s)
Embrión de Mamíferos/citología , Células Madre Embrionarias Humanas/citología , Enfermedad de Huntington/patología , Alelos , Animales , Células Cultivadas , Hibridación Genómica Comparativa , Genotipo , Prueba de Histocompatibilidad , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/trasplante , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/metabolismo , Cariotipo , Masculino , Ratones , Ratones SCID , Repeticiones de Microsatélite/genética , Microscopía Fluorescente , Teratoma/metabolismo , Teratoma/patología , Factores de Transcripción/metabolismo , Trasplante HeterólogoRESUMEN
The Genea066 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying expansion of CCTG repeats in exon 1 of the ZNF9 gene, indicative of Myotonic Dystrophy Type 2 (DM2). 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, 88% of cells expressed Nanog, 97% Oct4, 80% Tra1-60 and 99% SSEA4 and gave a Pluritest Pluripotency score of 31.3, Novelty of 1.22. The cell line was negative for Mycoplasma and visible contamination.