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Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment

(2019) STEM CELL REPORTS. 13(1). p.163-176
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Abstract
Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-beta- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic.
Keywords
COPY NUMBER, GENE-EXPRESSION, HUMAN ES, LINES, DIFFERENTIATION, CULTURE, INSTABILITY, DERIVATION, SURVIVAL, REVEALS

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Chicago
Markouli, C., E. Couvreu De Deckersberg, M. Regin, H. T. Nguyen, F. Zambelli, A. Keller, D. Dziedzicka, et al. 2019. “Gain of 20q11.21 in Human Pluripotent Stem Cells Impairs TGF-β-dependent Neuroectodermal Commitment.” Stem Cell Reports 13 (1): 163–176.
APA
Markouli, C., De Deckersberg, E. C., Regin, M., Nguyen, H. T., Zambelli, F., Keller, A., Dziedzicka, D., et al. (2019). Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment. STEM CELL REPORTS, 13(1), 163–176.
Vancouver
1.
Markouli C, De Deckersberg EC, Regin M, Nguyen HT, Zambelli F, Keller A, et al. Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment. STEM CELL REPORTS. 2019;13(1):163–76.
MLA
Markouli, C. et al. “Gain of 20q11.21 in Human Pluripotent Stem Cells Impairs TGF-β-dependent Neuroectodermal Commitment.” STEM CELL REPORTS 13.1 (2019): 163–176. Print.
@article{8624387,
  abstract     = {Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-beta- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic.},
  author       = {Markouli, C. and De Deckersberg, E. Couvreu and Regin, M. and Nguyen, H. T. and Zambelli, F. and Keller, A. and Dziedzicka, D. and De Kock, J. and Tilleman, Laurentijn and Van Nieuwerburgh, Filip and Franceschini, L. and Sermon, K. and Geens, M. and Spits, C.},
  issn         = {2213-6711},
  journal      = {STEM CELL REPORTS},
  keywords     = {COPY NUMBER,GENE-EXPRESSION,HUMAN ES,LINES,DIFFERENTIATION,CULTURE,INSTABILITY,DERIVATION,SURVIVAL,REVEALS},
  language     = {eng},
  number       = {1},
  pages        = {163--176},
  title        = {Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2019.05.005},
  volume       = {13},
  year         = {2019},
}

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