Engineering artificial signaling centers to polarize embryoid body differentiation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Dorthe R Petersen
  • Carsten Gustavsen
  • Søren Refsgård Lindskog
  • Mark A Magnuson
  • Kenneth S Zaret
  • Serup, Palle
Embryonic stem (ES) cells differentiating as aggregates self-organize dependent on Wnt signaling that is initially localized to discrete sites in the aggregate. As differentiation proceeds, Wnt signaling expands to most of the aggregates, thus resulting in widespread differentiation of mesendodermal progenitors. This process resembles primitive streak formation, but the lack of organized positional information makes the differentiating aggregates develop in a disorganized fashion. Here, we report that exogenous, cellular signaling sources can control the site where differentiation initiates in ES cell aggregates. Fibroblasts engineered to express cadherins are assembled with ES cells to form composite aggregates where the fibroblasts are positioned as a discrete pole. When engineered to express secreted Wnt agonists or antagonists, this pole functions to localize signaling in a way that polarizes the differentiating aggregates. The use of cell adhesion molecules to control morphology of developing stem cell aggregates should be widely applicable in tissue engineering.
OriginalsprogEngelsk
TidsskriftStem Cells and Development
Vol/bind21
Udgave nummer4
Sider (fra-til)647-53
Antal sider7
ISSN1547-3287
DOI
StatusUdgivet - 1 mar. 2012
Eksternt udgivetJa

ID: 46474410