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Derivation of Mouse Trophoblast Stem Cells from Blastocysts
10:19

Derivation of Mouse Trophoblast Stem Cells from Blastocysts

Published on: June 8, 2010

An Shp2/SFK/Ras/Erk signaling pathway controls trophoblast stem cell survival

Wentian Yang1, Lori D Klaman, Binbin Chen

  • 1Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. wyang@bidmc.harvard.edu

Developmental Cell
|March 7, 2006
PubMed

Insights

Shp2 is crucial for early embryonic development and stem cell survival. Its absence disrupts fibroblast growth factor-4 (FGF4) signaling, leading to apoptosis and impaired trophoblast stem cell proliferation.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Signaling

Background:

  • Growth factors are essential for regulating stem cell survival and proliferation.
  • The role of Shp2 (Ptpn11), a key receptor tyrosine kinase signaling component, in early development is not fully understood.

Purpose of the Study:

  • To investigate the function of Shp2 in early embryonic development and trophoblast stem (TS) cell survival.
  • To elucidate the molecular mechanism by which Shp2 controls stem cell proliferation and apoptosis.

Main Methods:

  • Analysis of Shp2 null mutant mice and Shp2-deleted TS cells.
  • Molecular marker analysis to assess lineage specification and expansion.
  • Investigation of the Src/Ras/Erk signaling pathway and its downstream targets.

Main Results:

  • Shp2 null embryos exhibit peri-implantation lethality and TS cell apoptosis.
  • Shp2 is essential for FGF4-mediated activation of the Src/Ras/Erk pathway.
  • Shp2 controls the phosphorylation and destabilization of the proapoptotic protein Bim, impacting TS cell survival.

Conclusions:

  • Shp2 plays a critical role in FGF4-dependent trophoblast stem cell survival and proliferation.
  • The FGF4-Shp2-Src/Ras/Erk-Bim pathway is a key mechanism regulating stem cell apoptosis and survival.

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