Related Experiment Video
Updated: May 16, 2026
10:32
Cell Surface Marker Mediated Purification of iPS Cell Intermediates from a Reprogrammable Mouse Model
Published on: September 6, 2014
A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network
Azadeh Golipour1, Laurent David, Yu Liu
1Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.
Cell Stem Cell
|December 11, 2012
Summary
Maturation and stabilization of induced pluripotent stem cells require transgene removal. A specific gene signature in stabilization-competent cells facilitates this transition to pluripotency and transgene independence.
Area of Science:
- Stem cell reprogramming
- Epigenetics
- Gene regulation
Background:
- Somatic cell reprogramming to pluripotency involves Oct4, Klf4, Myc, and Sox2 expression.
- Reprogramming progresses through distinct phases: maturation and stabilization.
Purpose of the Study:
- Investigate the molecular mechanisms governing the later stages of reprogramming, specifically maturation and stabilization.
- Determine the role of transgene expression removal in achieving pluripotency.
- Identify molecular signatures associated with successful reprogramming.
Main Methods:
- Focus on the maturation and stabilization phases of induced pluripotent stem cell (iPSC) generation.
- Utilize clonal analysis to differentiate between stabilization-competent (SC) and stabilization-incompetent (SI) cells.
- Perform gene expression profiling and functional analysis of SC signature genes.
Main Results:
- Transgene expression removal is crucial for the stabilization phase and pluripotency acquisition.
- SC clones exhibit a distinct competency gene-expression signature late in maturation.
- SC signature genes enhance the transition to stabilization and are vital for pluripotency maintenance.
Conclusions:
- Pluripotency acquisition and maintenance are governed by separate molecular networks.
- A novel regulatory program is essential for transitioning to transgene independence during reprogramming.
- Distinct molecular programs regulate the acquisition and maintenance of pluripotency.
Related Concept Videos
01:29Somatic to iPS Cell Reprogramming
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
01:24Methods of Nuclear Reprogramming
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
01:14Introduction to Nuclear Reprogramming
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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...