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TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.

Avior Y, Biancotti JC, Benvenisty N - Stem Cell Reports (2015)

Bottom Line: Teratoma formation is the gold standard assay for testing the capacity of human pluripotent stem cells to differentiate into all embryonic germ layers.Using gene expression data from a wide variety of cells, we created a scorecard representing tissues from all germ layers and extraembryonic tissues.Chromosomally aberrant teratomas show a significantly different gene expression signature from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, congruent with human chromosomal syndromes.

View Article: PubMed Central - PubMed

Affiliation: The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

No MeSH data available.


Related in: MedlinePlus

Tissue Classification of Genes Expressed Differently between WT and Aberrant TeratomasNumber of genes differentially expressed in chromosomally aberrant teratomas compared with teratomas initiated from diploid cells. Gene were considered differentially expressed when changed over 2-fold compared with control (∗p < 0.001). Teratomas from cells carrying trisomy of chromosome 12 (T12, n = 5) showed a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint as well as downregulated genes enriched for liver and fetal liver, colon, small intestine, lung, and skeletal muscle compared with WT teratomas (n = 5). In contrast, teratomas from cells carrying trisomy of chromosome 21 (T21, n = 4) showed significant number of downregulated genes specific for skeletal muscle only, with a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint.
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fig4: Tissue Classification of Genes Expressed Differently between WT and Aberrant TeratomasNumber of genes differentially expressed in chromosomally aberrant teratomas compared with teratomas initiated from diploid cells. Gene were considered differentially expressed when changed over 2-fold compared with control (∗p < 0.001). Teratomas from cells carrying trisomy of chromosome 12 (T12, n = 5) showed a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint as well as downregulated genes enriched for liver and fetal liver, colon, small intestine, lung, and skeletal muscle compared with WT teratomas (n = 5). In contrast, teratomas from cells carrying trisomy of chromosome 21 (T21, n = 4) showed significant number of downregulated genes specific for skeletal muscle only, with a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint.

Mentions: We therefore used another more sensitive bioinformatic strategy, establishing lists of the 200 most expressed genes in each tissue and looking for the ones most altered in chromosomally aberrant teratomas (Figure 4). In this analysis, trisomy 12-derived teratomas show a significant number of upregulated genes enriched for joint, spinal cord, brain, and fetal brain (p < 0.001) and a significant number of downregulated genes enriched for skeletal muscle, lung, small intestine, colon, fetal liver, and liver (p < 0.001) compared with normal karyotype teratomas. This wide set of gene expression alteration might suggest a pleiotropic effect of trisomy 12 on developmental patterns, contributing to its embryonic lethality. In contrast, teratomas initiated from cells with trisomy 21 show a more modest distortion of gene expression with a significant number of upregulated genes enriched for brain, fetal brain, and spinal cord (p < 0.001), as well as for joint, and a significant number of downregulated genes for skeletal muscle only compared with normal karyotype teratomas. The upregulation in brain genes in these teratomas is compatible with the neural phenotypes (such as mental impairment) observed in Down syndrome patients.


TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.

Avior Y, Biancotti JC, Benvenisty N - Stem Cell Reports (2015)

Tissue Classification of Genes Expressed Differently between WT and Aberrant TeratomasNumber of genes differentially expressed in chromosomally aberrant teratomas compared with teratomas initiated from diploid cells. Gene were considered differentially expressed when changed over 2-fold compared with control (∗p < 0.001). Teratomas from cells carrying trisomy of chromosome 12 (T12, n = 5) showed a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint as well as downregulated genes enriched for liver and fetal liver, colon, small intestine, lung, and skeletal muscle compared with WT teratomas (n = 5). In contrast, teratomas from cells carrying trisomy of chromosome 21 (T21, n = 4) showed significant number of downregulated genes specific for skeletal muscle only, with a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint.
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fig4: Tissue Classification of Genes Expressed Differently between WT and Aberrant TeratomasNumber of genes differentially expressed in chromosomally aberrant teratomas compared with teratomas initiated from diploid cells. Gene were considered differentially expressed when changed over 2-fold compared with control (∗p < 0.001). Teratomas from cells carrying trisomy of chromosome 12 (T12, n = 5) showed a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint as well as downregulated genes enriched for liver and fetal liver, colon, small intestine, lung, and skeletal muscle compared with WT teratomas (n = 5). In contrast, teratomas from cells carrying trisomy of chromosome 21 (T21, n = 4) showed significant number of downregulated genes specific for skeletal muscle only, with a significant number of upregulated genes enriched for brain, fetal brain, spinal cord, and joint.
Mentions: We therefore used another more sensitive bioinformatic strategy, establishing lists of the 200 most expressed genes in each tissue and looking for the ones most altered in chromosomally aberrant teratomas (Figure 4). In this analysis, trisomy 12-derived teratomas show a significant number of upregulated genes enriched for joint, spinal cord, brain, and fetal brain (p < 0.001) and a significant number of downregulated genes enriched for skeletal muscle, lung, small intestine, colon, fetal liver, and liver (p < 0.001) compared with normal karyotype teratomas. This wide set of gene expression alteration might suggest a pleiotropic effect of trisomy 12 on developmental patterns, contributing to its embryonic lethality. In contrast, teratomas initiated from cells with trisomy 21 show a more modest distortion of gene expression with a significant number of upregulated genes enriched for brain, fetal brain, and spinal cord (p < 0.001), as well as for joint, and a significant number of downregulated genes for skeletal muscle only compared with normal karyotype teratomas. The upregulation in brain genes in these teratomas is compatible with the neural phenotypes (such as mental impairment) observed in Down syndrome patients.

Bottom Line: Teratoma formation is the gold standard assay for testing the capacity of human pluripotent stem cells to differentiate into all embryonic germ layers.Using gene expression data from a wide variety of cells, we created a scorecard representing tissues from all germ layers and extraembryonic tissues.Chromosomally aberrant teratomas show a significantly different gene expression signature from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, congruent with human chromosomal syndromes.

View Article: PubMed Central - PubMed

Affiliation: The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

No MeSH data available.


Related in: MedlinePlus