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Preparation of Mouse Embryonic Fibroblast Cells Suitable for Culturing Human Embryonic and Induced Pluripotent Stem Cells
Published on: June 21, 2012
Cell-cell signaling through NOTCH regulates human embryonic stem cell proliferation
Victoria Fox1, Paul J Gokhale, James R Walsh
1Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.
Stem Cells (Dayton, Ohio)
|December 7, 2007
Summary
NOTCH signaling is crucial for the proliferation of human embryonal carcinoma (EC) and embryonic stem (ES) cells. Blocking this pathway significantly reduces the growth of these critical cell types in vitro.
Area of Science:
- Stem Cell Biology
- Cell Signaling
- Cancer Research
Background:
- Human embryonic stem (ES) cells and embryonal carcinoma (EC) cells require cell-cell contact for growth, unlike mouse ES cells.
- NOTCH signaling, mediated by DELTA/JAGGED ligands, is known to regulate self-renewal in various stem cell systems.
Purpose of the Study:
- To investigate the role of NOTCH signaling in the maintenance and proliferation of human ES and EC cells.
- To determine if NOTCH pathway activation is necessary for the in vitro growth of these human cell types.
Main Methods:
- Detection of cleaved NOTCH1 and NOTCH2 intracellular domains in human EC and ES cell lines.
- Small interfering RNA (siRNA) knockdown of NOTCH1, NOTCH2, and CBF-1.
- Inhibition of NOTCH signaling using the gamma-secretase inhibitor L-685,458.
Main Results:
- NOTCH signaling was confirmed to be active in human EC and ES cells.
- siRNA knockdown and gamma-secretase inhibition significantly reduced human EC cell proliferation and downstream gene expression.
- Gamma-secretase inhibition also reduced human ES cell growth without inducing differentiation.
Conclusions:
- Cell-cell signaling via the NOTCH pathway is essential for the in vitro proliferation of human EC and ES cells.
- The NOTCH system provides a critical regulatory cue for maintaining the growth of these stem and cancer cells.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role 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...
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...
01:14Maintenance 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...
01:26Stem Cell Niche
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
00:57Embryonic Stem Cells
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...