Related Experiment Video
Updated: Apr 21, 2026
11:38
RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
11.5K
Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and
Simon E Vidal1, Bhishma Amlani1, Taotao Chen1
1The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Stem Cell Reports
|November 1, 2014
Summary
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is challenging. This study reveals cell-specific signaling pathway modulation, like TGF-β inhibition and Wnt activation, enhances reprogramming efficiency and synchrony.
Area of Science:
- Cell Biology
- Stem Cell Research
- Developmental Biology
Background:
- Somatic cell differentiation poses challenges for induced pluripotent stem cell (iPSC) generation.
- Understanding cell-type-specific reprogramming efficiencies is crucial for advancing regenerative medicine.
Purpose of the Study:
- To investigate the impact of combined signaling pathway modulation on somatic cell reprogramming.
- To elucidate the reasons behind differential reprogramming efficiencies across various cell types.
Main Methods:
- Modulation of transforming growth factor β (TGF-β) and Wnt signaling pathways.
- Co-culture with ascorbic acid and reprogramming factors.
- Analysis of pluripotency gene reactivation and chromatin modification.
Main Results:
- Inhibition of TGF-β plus Wnt activation reprogrammed >80% of murine fibroblasts within one week.
- Hepatic and blood progenitors achieved near 100% reprogramming with TGF-β inhibition or Wnt activation alone, respectively.
- Blood progenitors exhibited synchronous reactivation of pluripotency loci, linked to chromatin modifiers and reduced TGF-β/MAPK activity.
Conclusions:
- Cell-type-specific signaling pathway modulation is key for efficient and synchronous somatic cell reprogramming.
- Intrinsic properties of blood progenitors facilitate rapid pluripotency acquisition.
- These findings define distinct requirements for reprogramming diverse somatic cell types into iPSCs.
Related Concept Videos
02:33Combinatorial Gene Control
8.4K
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...
8.4K
01:29Somatic to iPS Cell Reprogramming
2.0K
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...
2.0K
01:32Chromatin Modification in iPS Cells
1.5K
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...
1.5K
01:24Methods of Nuclear Reprogramming
1.4K
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...
1.4K
01:13Induced Pluripotent Stem Cells
22.8K
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...
22.8K
01:13Induced Pluripotent Stem Cells
3.4K
3.4K