Choice of factors and medium impinge on success of ESC to TSC conversion

Kaiser, Franziska; Kubaczka, Caroline; Graf, Monika; Langer, Nina; Langkabel, Jan; Arévalo, Lena; Schorle, Hubert

doi:10.1016/j.placenta.2019.12.017

Cited by 8 publications

(12 citation statements)

References 35 publications

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“…Thereby, the structures generated using the presented method resemble "ETX-embryos" as previously described (Sozen et al, 2018;Zhang et al, 2019). As previously shown, transcription factor-mediated reprogramming can be used to generate iTSC and iXEN cells from mESC (Wamaitha et al, 2015;Kaiser et al, 2020). Here, we demonstrate that reprogramming towards iTSCand iXEN cell-fate in 3D cell culture not only leads to the induction of the respective celllineage but also results in compartmented embryo-like structures.…”

Section: Discussionmentioning

confidence: 54%

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results In Embryo-like Structuresmentioning

confidence: 95%

“…Here, reprogramming of ESC to iTSC was achieved by induction of Cdx2, Tfap2c, Eomes, Gata3, and Ets2 (Kaiser et al, 2020) and reprogramming of ESC to iXEN cells is possible by overexpression of Gata6 (Wamaitha et al, 2015;Ngondo et al, 2018). To test whether such transcription factor-mediated cellular reprogramming in defined ESC lines is sufficient to generate synthetic embryo-like structures, we used our 5-Factor ESC line (5F-ESC) carrying doxycycline-inducible transgenes of Cdx2, Tfap2c, Eomes, Gata3, and Ets2 (Kaiser et al, 2020) in combination with an ESC line carrying a doxycycline-inducible Gata6 transgene, (iGATA6 ESC) (Ngondo et al, 2018) in addition to an ESC line carrying an Oct3/4 promoter-driven GFP cassette, termed here 'Kermit ESC'. While the 5F-ESCs give rise to iTSC (Kaiser et al, 2020), iGATA6 ESCs were predicted to reprogram to iXEN (Wamaitha et al, 2015;Ngondo et al, 2018) and Kermit ESCs to ICM derivatives.…”

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results Imentioning

confidence: 99%

“…In recent years, we and others demonstrated that ESC can be reprogrammed to bona fide TSC and XEN cells (Wamaitha et al, 2015;Kaiser et al, 2020). Here, reprogramming of ESC to iTSC was achieved by induction of Cdx2, Tfap2c, Eomes, Gata3, and Ets2 (Kaiser et al, 2020) and reprogramming of ESC to iXEN cells is possible by overexpression of Gata6 (Wamaitha et al, 2015;Ngondo et al, 2018). To test whether such transcription factor-mediated cellular reprogramming in defined ESC lines is sufficient to generate synthetic embryo-like structures, we used our 5-Factor ESC line (5F-ESC) carrying doxycycline-inducible transgenes of Cdx2, Tfap2c, Eomes, Gata3, and Ets2 (Kaiser et al, 2020) in combination with an ESC line carrying a doxycycline-inducible Gata6 transgene, (iGATA6 ESC) (Ngondo et al, 2018) in addition to an ESC line carrying an Oct3/4 (which was not certified by peer review) is the author/funder.…”

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results In Embryo-like Structuresmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted January 25, 2021. ; https://doi.org/10.1101/2021.01.25.428068 doi: bioRxiv preprint promoter-driven GFP cassette, termed here 'Kermit ESC'. While the 5F-ESCs give rise to iTSC (Kaiser et al, 2020), iGATA6 ESCs were predicted to reprogram to iXEN (Wamaitha et al, 2015;Ngondo et al, 2018) and Kermit ESCs to ICM derivatives. All cells were grown under standard ESC culture conditions (FBS, 2i/LIF).…”

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results In Embryo-like Structuresmentioning

confidence: 99%

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Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs

Langkabel

Horne

Bonaguro

et al. 2021

Preprint

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SummaryBlastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that synthetic embryo-like structures are generated solely based on transcription factor-mediated molecular reprogramming of embryonic stem cells in a simple 3D co-culture system. ESCs in these cultures self-organize into elongated, compartmentalized synthetic embryo-like structures over the course of reprogramming exhibiting anterior visceral endoderm formation and symmetry breaking. Single-cell RNA-Seq reveals transcriptional profiles resembling epiblast, visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5–E5.5. Within the epiblast, compartment marker gene expression supports primordial germ cell specification. After transplantation, synthetic embryo-like structures implant in uteri and initiate the formation of decidual tissues. This system allows for fast and reproducible generation of synthetic embryo-like structures, providing further insights into synthetic embryology.

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Section: Discussionmentioning

confidence: 54%

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results In Embryo-like Structuresmentioning

confidence: 95%

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results Imentioning

confidence: 99%

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results In Embryo-like Structuresmentioning

confidence: 99%

Section: Reprogramming Of Escs In Parallel To 3d Co-culture Results In Embryo-like Structuresmentioning

confidence: 99%

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Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs

Langkabel

Horne

Bonaguro

et al. 2021

Preprint

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Unlocking trophectoderm mysteries: In vivo and in vitro perspectives on human and mouse trophoblast fate induction

Azagury,

Buganim

2024

Developmental Cell

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Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs

et al. 2021

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Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5–E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.

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Choice of factors and medium impinge on success of ESC to TSC conversion

Cited by 8 publications

References 35 publications

Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs

Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs

Unlocking trophectoderm mysteries: In vivo and in vitro perspectives on human and mouse trophoblast fate induction

Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs

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