Differentiation of Embryonic Stem Cells

Introduction

Embryonic stem (ES) cells have been derived for several mammals from the inner cell mass (ICM) of a preimplantation blastocyst. These cells have the property to divide unlimitedly and remain undifferentiated in vitro, a process controlled by factors such as NANOG and OCT4.
In specific culture conditions they are able to differentiate into any cell type of the adult body, a capacity known as pluripotency. These features make ES cells a potential alternative for organ transplantation. It has been shown in human as well as mouse ES cells that Retinoic Acid specifically induces neuronal cells, and dimethylsulfoxide has been shown to induce different mesodermal cell derivatives, including spontaneously beating structures, mimicking the beating of the heart in the embryo.
More recently, growth factors expressed in the developing embryo have been successfully applied on mouse ES cells to obtain, for example, endodermal or neuronal cells. Therefore, a parallel can be drawn between the developing embryo and ES cell differentiation.

Research topics

Since the differentiation of ES cells mimmicks the early development, we are using ES cells as a developmental approach similar to the animal cap assay in frogs.

We are studying how are the mesoderm and neuroectoderm germ layer induced.

ES differentiation

We aim at:

  • Identifying the secreted factors responsible for the early induction of the mesoderm and neuroblasts,
  • Studying the patterning effect (antero-posterior; dorso-ventral) of the secreted factors alone or in combination
  • Analyzing the integration of multiple signals to induce specific tissues

For that purpose, we analyse by microarrays, qRT-PCR and in situ hybridization the induction of marker genes in ES cells treated with the different signaling factors (Wnt, BMP, Nodal, FGF) or their secreted antagonists (Frzb, Noggin, Cerberus, ...).

ES flow

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