Activin A Efficiently Specifies Definitive Endoderm from Human Embryonic Stem Cells Only When Phosphatidylinositol 3‐Kinase Signaling Is Suppressed

@article{McLean2007ActivinAE,
  title={Activin A Efficiently Specifies Definitive Endoderm from Human Embryonic Stem Cells Only When Phosphatidylinositol 3‐Kinase Signaling Is Suppressed},
  author={Amanda B McLean and Kevin A. D’Amour and Karen Louise Jones and Malini Krishnamoorthy and Michael Kulik and David M Reynolds and Allan M. Sheppard and Hui-qiong Liu and Ying Xu and Emmanuel E. Baetge and Stephen Dalton},
  journal={STEM CELLS},
  year={2007},
  volume={25}
}
Human ESCs (hESCs) respond to signals that determine their pluripotency, proliferation, survival, and differentiation status. In this report, we demonstrate that phosphatidylinositol 3‐kinase (PI3K) antagonizes the ability of hESCs to differentiate in response to transforming growth factor β family members such as Activin A and Nodal. Inhibition of PI3K signaling efficiently promotes differentiation of hESCs into mesendoderm and then definitive endoderm (DE) by allowing them to be specified by… 

The Generation of Definitive Endoderm from Human Embryonic Stem Cells is Initially Independent from Activin A but Requires Canonical Wnt-Signaling

The in vitro differentiation of human ES cells into definitive endoderm is initially independent from the activin A/TGF-beta pathway but requires high canonical Wnt-signaling activity.

Analysis of alternative signaling pathways of endoderm induction of human embryonic stem cells identifies context specific differences

Use of FGF2, W NT3A or PI3K inhibition with high activin A may serve well in definitive endoderm induction followed by WNT3A specific signaling to direct the definitiveendoderm into late endodermal lineages.

Insulin Redirects Differentiation from Cardiogenic Mesoderm and Endoderm to Neuroectoderm in Differentiating Human Embryonic Stem Cells

It is concluded that in hESC/END‐2 cocultures, insulin does not prevent differentiation but favors the neuroectodermal lineage at the expense of mesendodermal lineages.

Mechanistic characterisation of Activin/Smad and PI3K/mTOR crosstalk during the specification of definitive endoderm from human embryonic stem cells

These findings reveal a new and novel connection between the PI3K/mTOR and TGFβ/Activin pathways, which will greatly impact the understanding of both cell fate determination and the preservation of normal cellular functions.

Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling

The studies provide compelling evidence that Wnt3a signaling is important for coordinated hepatocellular function in vitro and in vivo and demonstrate that WNT3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation.

Guided Differentiation of Embryonic Stem Cells into Pdx1‐Expressing Regional‐Specific Definitive Endoderm

A detailed chronological analysis revealed that Activin, fibroblast growth factor, or bone morphogenetic protein signals are critical at various steps and that additional short‐range signals are required for differentiation into Pdx1‐expressing cells.
...

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