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Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation

Margot Van der Jeught (UGent) , Björn Heindryckx (UGent) , Thomas O'Leary (UGent) , Galbha Duggal (UGent) , Sabitri Ghimire (UGent) , Sylvie Lierman (UGent) , Nadine Van Roy (UGent) , Susana Marina Chuva de Sousa Lopes (UGent) , Tom Deroo (UGent) , Dieter Deforce (UGent) , et al.
(2014) HUMAN REPRODUCTION. 29(1). p.41-48
Author
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Abstract
Study question: Is there an effect of the TGFb inhibitor SB431542 (SB) on the epiblast compartment of human blastocysts, and does it affect subsequent human embryonic stem cell (hESC) derivation? Summary answer: SB increases the mean number of NANOG-positive cells in the inner cell mass (ICM), and allows for subsequent hESC derivation. What is known already: It is known that inhibition of TGFb by SB has a positive effect on mouse ESC self-renewal, while active TGFb signalling is needed for self-renewal of primed ESC. Study design, size, duration: From December 2011 until March 2012, 263 donated spare embryos were used from patients who had undergone IVF/ICSI in our centre. Participants/materials, setting, methods: Donated human embryos were cultured in the presence of SB or Activin A, and immunocytochemistry was performed on Day 6 blastocysts for NANOG and GATA6. Moreover, blastocysts were used for the derivation of hESC, with or without exposure to SB. Mmain results and the role of chance: Immunocytochemistry revealed a significantly higher number of NANOG-positive ICM cells in the SB group compared with the control (12.0+5.9 versus 6.1+4.7), while no difference was observed in the Activin A group compared with other groups (6.7+3.7). The number of GATA6-positive ICM cells did not differ between the SB, Activin A and control group (8.8+4.3, 8.0+4.6 and 7.2+4.0, respectively). Blocking TGFb signalling did not prevent subsequent hESC line derivation. Limitations, reasons for caution: The number of human blastocysts available for this study was too low to reveal if the observed increase in NANOG-positive epiblast cells after exposure to SB affected the efficiency of hESC derivation (12.5% compared with 16.7%). Wider implications of the findings: This work can contribute to the derivation of naive hESC lines in the future.
Keywords
GROWTH-FACTOR, PRIMITIVE ENDODERM, naive hESC, epiblast, human embryonic stem cell (hESC) derivation, human embryo development, TGF beta inhibition, MOUSE BLASTOCYST, RAT BLASTOCYSTS, SELF-RENEWAL, DIFFERENTIATION, PLURIPOTENCY, FGF, SEGREGATION, PATHWAY

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MLA
Van der Jeught, Margot, et al. “Treatment of Human Embryos with the TGFβ Inhibitor SB431542 Increases Epiblast Proliferation and Permits Successful Human Embryonic Stem Cell Derivation.” HUMAN REPRODUCTION, vol. 29, no. 1, 2014, pp. 41–48, doi:10.1093/humrep/det400.
APA
Van der Jeught, M., Heindryckx, B., O’Leary, T., Duggal, G., Ghimire, S., Lierman, S., … De Sutter, P. (2014). Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation. HUMAN REPRODUCTION, 29(1), 41–48. https://doi.org/10.1093/humrep/det400
Chicago author-date
Van der Jeught, Margot, Björn Heindryckx, Thomas O’Leary, Galbha Duggal, Sabitri Ghimire, Sylvie Lierman, Nadine Van Roy, et al. 2014. “Treatment of Human Embryos with the TGFβ Inhibitor SB431542 Increases Epiblast Proliferation and Permits Successful Human Embryonic Stem Cell Derivation.” HUMAN REPRODUCTION 29 (1): 41–48. https://doi.org/10.1093/humrep/det400.
Chicago author-date (all authors)
Van der Jeught, Margot, Björn Heindryckx, Thomas O’Leary, Galbha Duggal, Sabitri Ghimire, Sylvie Lierman, Nadine Van Roy, Susana Marina Chuva de Sousa Lopes, Tom Deroo, Dieter Deforce, and Petra De Sutter. 2014. “Treatment of Human Embryos with the TGFβ Inhibitor SB431542 Increases Epiblast Proliferation and Permits Successful Human Embryonic Stem Cell Derivation.” HUMAN REPRODUCTION 29 (1): 41–48. doi:10.1093/humrep/det400.
Vancouver
1.
Van der Jeught M, Heindryckx B, O’Leary T, Duggal G, Ghimire S, Lierman S, et al. Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation. HUMAN REPRODUCTION. 2014;29(1):41–8.
IEEE
[1]
M. Van der Jeught et al., “Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation,” HUMAN REPRODUCTION, vol. 29, no. 1, pp. 41–48, 2014.
@article{4295599,
  abstract     = {{Study question: Is there an effect of the TGFb inhibitor SB431542 (SB) on the epiblast compartment of human blastocysts, and does it affect subsequent human embryonic stem cell (hESC) derivation?
Summary answer: SB increases the mean number of NANOG-positive cells in the inner cell mass (ICM), and allows for subsequent hESC derivation.
What is known already: It is known that inhibition of TGFb by SB has a positive effect on mouse ESC self-renewal, while active TGFb signalling is needed for self-renewal of primed ESC.
Study design, size, duration: From December 2011 until March 2012, 263 donated spare embryos were used from patients who had undergone IVF/ICSI in our centre.
Participants/materials, setting, methods: Donated human embryos were cultured in the presence of SB or Activin A, and immunocytochemistry was performed on Day 6 blastocysts for NANOG and GATA6. Moreover, blastocysts were used for the derivation of hESC, with or without exposure to SB.
Mmain results and the role of chance: Immunocytochemistry revealed a significantly higher number of NANOG-positive ICM cells in the SB group compared with the control (12.0+5.9 versus 6.1+4.7), while no difference was observed in the Activin A group compared with other groups (6.7+3.7). The number of GATA6-positive ICM cells did not differ between the SB, Activin A and control group (8.8+4.3, 8.0+4.6 and 7.2+4.0, respectively). Blocking TGFb signalling did not prevent subsequent hESC line derivation.
Limitations, reasons for caution: The number of human blastocysts available for this study was too low to reveal if the observed increase in NANOG-positive epiblast cells after exposure to SB affected the efficiency of hESC derivation (12.5% compared with 16.7%).
Wider implications of the findings: This work can contribute to the derivation of naive hESC lines in the future.}},
  author       = {{Van der Jeught, Margot and Heindryckx, Björn and O'Leary, Thomas and Duggal, Galbha and Ghimire, Sabitri and Lierman, Sylvie and Van Roy, Nadine and Chuva de Sousa Lopes, Susana Marina and Deroo, Tom and Deforce, Dieter and De Sutter, Petra}},
  issn         = {{0268-1161}},
  journal      = {{HUMAN REPRODUCTION}},
  keywords     = {{GROWTH-FACTOR,PRIMITIVE ENDODERM,naive hESC,epiblast,human embryonic stem cell (hESC) derivation,human embryo development,TGF beta inhibition,MOUSE BLASTOCYST,RAT BLASTOCYSTS,SELF-RENEWAL,DIFFERENTIATION,PLURIPOTENCY,FGF,SEGREGATION,PATHWAY}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{41--48}},
  title        = {{Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation}},
  url          = {{http://doi.org/10.1093/humrep/det400}},
  volume       = {{29}},
  year         = {{2014}},
}
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