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Somatic to iPS Cell Reprogramming

Somatic 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...

Chromatin Modification in iPS Cells

Chromatin 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...

Maintenance of the ES Cell State

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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...

Methods of Nuclear Reprogramming

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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.

Introduction to Nuclear Reprogramming

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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...

Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells

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 cells are...

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Related Experiment Video

Updated: Jun 9, 2026

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells

Published on: November 26, 2018

Stat3 activation is limiting for reprogramming to ground state pluripotency.

Jian Yang¹, Anouk L van Oosten, Thorold W Theunissen

¹Wellcome Trust Centre for Stem Cell Research & Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK.

|September 1, 2010

Summary

Leukemia inhibitory factor (Lif) pathway activation via Jak/Stat3 signaling directly contributes to cellular reprogramming. Enhancing this pathway promotes the induction of pluripotency in stem cells and somatic cells.

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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors

In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors

Published on: December 17, 2013

Area of Science:

Stem cell biology
Molecular and Cellular Biology
Developmental Biology

Background:

Leukemia inhibitory factor (Lif) is crucial for maintaining pluripotency and self-renewal in embryonic and induced pluripotent stem cells.
Lif signaling activates the Janus kinase (Jak) and signal transducer and activator of transcription 3 (Stat3) pathway.
Epiblast stem cells (EpiSCs) express low levels of Lif receptor and Stat3, suggesting limited endogenous Jak/Stat3 activity.

Purpose of the Study:

To investigate the role of the Jak/Stat3 pathway in the induction of pluripotency.
To determine if activating Jak/Stat3 signaling can enhance cellular reprogramming.
To explore the potential of Jak/Stat3 activation as a limiting factor in reprogramming.

Main Methods:

Introduction of a granulocyte colony-stimulating factor (Gcsf)-responsive receptor (GY118F) into EpiSCs to activate Jak/Stat3.
Culture of reprogrammed cells in a ground state medium inhibiting MAPK signaling and glycogen synthase kinase.
Activation of a tamoxifen-regulatable Stat3 fusion protein (Stat3ER(T2)).
Utilizing the GY118F receptor to modulate Jak/Stat3 activity during somatic cell reprogramming.

Main Results:

Gcsf stimulation induced transcriptional resetting and functional reprogramming in EpiSCs upon transfer to ground state culture.
Activation of Stat3ER(T2) converted EpiSCs into chimera-competent induced pluripotent stem cells (iPSCs).
Enhancing Jak/Stat3 activity with Gcsf increased the frequency of progression to ground state pluripotency in incompletely reprogrammed neural stem cells and fibroblasts.

Conclusions:

The Jak/Stat3 signaling pathway plays a direct role in molecular reprogramming.
Activation of the Jak/Stat3 pathway is a critical and potentially limiting component in the induction of pluripotency.
Targeting Jak/Stat3 signaling offers a strategy to improve the efficiency of cellular reprogramming.