Reference - Detail
| RRC ID | 4346 |
|---|---|
| Author | Sumi T, Tsuneyoshi N, Nakatsuji N, Suemori H. |
| Title | Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/beta-catenin, Activin/Nodal and BMP signaling. |
| Journal | Development |
| Abstract |
The canonical Wnt/beta-catenin signaling has remarkably diverse roles in embryonic development, stem cell self-renewal and cancer progression. Here, we show that stabilized expression of beta-catenin perturbed human embryonic stem (hES)-cell self-renewal, such that up to 80% of the hES cells developed into the primitive streak (PS)/mesoderm progenitors, reminiscent of early mammalian embryogenesis. The formation of the PS/mesoderm progenitors essentially depended on the cooperative action of beta-catenin together with Activin/Nodal and BMP signaling pathways. Intriguingly, blockade of BMP signaling completely abolished mesoderm generation, and induced a cell fate change towards the anterior PS progenitors. The PI3-kinase/Akt, but not MAPK, signaling pathway had a crucial role in the anterior PS specification, at least in part, by enhancing beta-catenin stability. In addition, Activin/Nodal and Wnt/beta-catenin signaling synergistically induced the generation and specification of the anterior PS/endoderm. Taken together, our findings clearly demonstrate that the orchestrated balance of Activin/Nodal and BMP signaling defines the cell fate of the nascent PS induced by canonical Wnt/beta-catenin signaling in hES cells. |
| Volume | 135(17) |
| Pages | 2969-79 |
| Published | 2008-9-1 |
| DOI | 10.1242/dev.021121 |
| PII | dev.021121 |
| PMID | 18667462 |
| MeSH | Activins / metabolism* Bone Morphogenetic Proteins / metabolism* Bone Morphogenetic Proteins / pharmacology Cell Differentiation / drug effects Cell Lineage* / drug effects Embryonic Stem Cells / cytology* Embryonic Stem Cells / drug effects Endoderm / cytology Endoderm / drug effects Endoderm / enzymology Humans MAP Kinase Signaling System / drug effects Mesoderm / cytology Mesoderm / drug effects Mesoderm / embryology Mesoderm / enzymology Nodal Protein Phosphatidylinositol 3-Kinases / metabolism Phosphoinositide-3 Kinase Inhibitors Primitive Streak / cytology Primitive Streak / drug effects Protein Kinase Inhibitors / pharmacology Signal Transduction / drug effects Thermodynamics Time Factors Transforming Growth Factor beta / metabolism* Wnt Proteins / metabolism* beta Catenin / metabolism* |
| IF | 5.611 |
| Times Cited | 211 |
| WOS Category | DEVELOPMENTAL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 27 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human embryonic stem cells | KhES-1 KhES-3 |