Related Experiment Video
Updated: Jan 3, 2026
13:02
Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4
Published on: April 7, 2008
36.7K
Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4
Zhaojun An1, Peng Liu2, Jiashun Zheng3
1Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Science, Tsinghua University, Beijing 100084, China.
Cell Reports
|November 14, 2019
Summary
Sox2 and Klf4 can reprogram cells into induced pluripotent stem cells (iPSCs) without Oct4. Their specific ratio is crucial for activating pluripotency networks and epigenetic remodeling, regardless of cell origin.
Area of Science:
- Stem cell biology
- Epigenetics
- Cellular reprogramming
Background:
- Oct4, Sox2, Klf4, and c-Myc are established factors for inducing pluripotency.
- Oct4 has historically been considered the central reprogramming factor.
- The precise roles and sufficiency of individual factors remain areas of investigation.
Purpose of the Study:
- To investigate the core function of Sox2 and Klf4 in cellular reprogramming.
- To determine if Sox2 and Klf4 alone can induce pluripotency without Oct4.
- To explore the mechanism of Sox2 and Klf4-mediated reprogramming and its dependence on cell origin.
Main Methods:
- Utilized polycistronic expression of Sox2 and Klf4 to reprogram somatic cells.
- Analyzed the stoichiometry of Sox2 and Klf4 expression.
- Performed genome-wide binding analysis and epigenetic profiling.
- Compared reprogramming efficiency across different cell types (fibroblasts and neural progenitors).
Main Results:
- Polycistronic Sox2 and Klf4 expression successfully induced pluripotency in the absence of Oct4.
- The stoichiometric ratio of Sox2 and Klf4 was critical for reprogramming efficiency.
- Sox2 and Klf4 cooperatively targeted genomic regions, driving epigenetic modifications and activating pluripotency genes.
- Reprogramming trajectories and efficiency were similar for mesodermal (fibroblasts) and ectodermal (neural progenitor) cells.
Conclusions:
- Sox2 and Klf4 possess a core function in inducing pluripotency, challenging the central role of Oct4.
- The mechanism of Sox2 and Klf4-mediated reprogramming is independent of the cell's germ layer origin.
- Precise control over Sox2 and Klf4 stoichiometry is essential for efficient induction of pluripotency.
Related Concept Videos
01:29Somatic to iPS Cell Reprogramming
2.5K
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...
2.5K
02:33Combinatorial Gene Control
9.4K
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...
9.4K
01:24Methods of Nuclear Reprogramming
2.1K
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...
2.1K
01:13Induced Pluripotent Stem Cells
27.2K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
27.2K
01:06Induced Pluripotent Stem Cells
5.3K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
5.3K
01:14Maintenance of the ES Cell State
2.6K
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...
2.6K