Related Experiment Video

Updated: May 31, 2026

The use of SC1 (Pluripotin) to Support mESC Self-renewal in the Absence of LIF
05:58

The use of SC1 (Pluripotin) to Support mESC Self-renewal in the Absence of LIF

Published on: November 18, 2009

Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal

Fei Yi1, Laura Pereira, Jackson A Hoffman

  • 1Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland Avenue, MBRB 2270, M/C 669, Chicago, Illinois 60607, USA.

Nature Cell Biology
|June 21, 2011
PubMed

Insights

Wnt signaling regulates mouse embryonic stem cell self-renewal by inhibiting Tcf3, a repressor. Tcf3 and Tcf1 recruit beta-catenin to key gene sites, linking Wnt effects to the Oct4/Sox2/Nanog network.

Area of Science:

  • Stem cell biology
  • Molecular and developmental biology
  • Epigenetics and gene regulation

Background:

  • Tcf3 co-occupies chromatin with Oct4, Sox2, and Nanog in mouse embryonic stem cells (ESCs).
  • Tcf3's role in Wnt-dependent ESC self-renewal stimulation is poorly understood.
  • Conventional models propose Tcf proteins activate target genes via beta-catenin binding.

Purpose of the Study:

  • To investigate the antagonistic relationship between Wnt3a and Tcf3 in regulating ESC self-renewal.
  • To elucidate the downstream effects of Wnt signaling on Tcf3 function.
  • To determine the role of Tcf3 and Tcf1 in recruiting beta-catenin to ESC chromatin.

Main Methods:

  • Genetic ablation of Tcf3 in mouse ESCs.
  • Analysis of Wnt3a and GSK3 inhibition requirements for ESC self-renewal.
  • Chromatin immunoprecipitation assays to assess Tcf3, Tcf1, and beta-catenin binding to Oct4 sites.

Main Results:

  • Genetic ablation of Tcf3 obviates the need for Wnt3a or GSK3 inhibition for ESC self-renewal.
  • Wnt signaling inhibition of Tcf3 repressor activity is a necessary downstream effect.
  • Tcf3-beta-catenin and Tcf1-beta-catenin interactions contribute to Wnt-stimulated self-renewal and gene expression.
  • Tcf3 and Tcf1 recruit Wnt-stabilized beta-catenin to Oct4 binding sites on ESC chromatin.

Conclusions:

  • An antagonistic relationship between Wnt3a and Tcf3 regulates ESC self-renewal.
  • Wnt signaling promotes ESC self-renewal by inhibiting the repressor Tcf3.
  • This study reveals a molecular link between Wnt signaling and the Oct4/Sox2/Nanog network in ESCs.

More Related Videos

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies09:04

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

Published on: April 22, 2017

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...