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

Oleh:

Jeught, Margot Van der ; Heindryckx, Bjorn ; O Leary, Thomas ; Duggal, Galbha ; Ghimire, Sabitri

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 29 no. 01 (Jan. 2014), page 41-48.
Topik: TGFß inhibition; human embryo development; epiblast; human embryonic stem cell (hESC) derivation; naive hESC

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Perpustakaan FK Nomor Panggil: H07.K.2014.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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STUDY QUESTION Is there an effect of the TGFß 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 TGFß by SB has a positive effect on mouse ESC self-renewal, while active TGFß 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. MAIN 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 TGFß 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.

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