Engineering artificial signaling centers to polarize embryoid body differentiation

TY - JOUR

T1 - Engineering artificial signaling centers to polarize embryoid body differentiation

AU - Petersen, Dorthe R

AU - Gustavsen, Carsten

AU - Lindskog, Søren Refsgård

AU - Magnuson, Mark A

AU - Zaret, Kenneth S

AU - Serup, Palle

PY - 2012/3/1

Y1 - 2012/3/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Differentiation

KW - Embryoid Bodies

KW - L Cells (Cell Line)

KW - Mice

KW - Tissue Engineering

U2 - 10.1089/scd.2011.0344

DO - 10.1089/scd.2011.0344

M3 - Journal article

C2 - 21958075

SN - 1547-3287

VL - 21

SP - 647

EP - 653

JO - Stem Cells and Development

JF - Stem Cells and Development

IS - 4

ER -