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Driving pluripotency and reprogramming: nuclear receptors at the helm
Kevin Andrew Uy Gonzales1, Huck-Hui Ng
1Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore.
Seminars in Cell & Developmental Biology
|August 7, 2013
Summary
Nuclear receptors are key transcription factors regulating embryonic stem cell pluripotency. This review explores their roles in self-renewal, differentiation, and reprogramming, offering future research directions.
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Genetics
Background:
- Cellular identity is governed by molecular interactions, including transcription factors.
- Transcriptional circuitry is crucial for maintaining and changing cell states, especially pluripotency.
- Nuclear receptors are emerging as significant regulators in pluripotency networks.
Purpose of the Study:
- To review the critical roles of nuclear receptors in embryonic stem cell biology.
- To highlight recent advancements in understanding nuclear receptors in pluripotency.
- To provide an outlook on future stem cell and nuclear receptor research.
Main Methods:
- Literature review of scientific publications.
- Analysis of existing data on nuclear receptor function.
- Synthesis of current knowledge on pluripotency regulation.
Main Results:
- Nuclear receptors significantly influence embryonic stem cell self-renewal.
- These receptors play vital roles in stem cell differentiation pathways.
- Nuclear receptors are implicated in cellular reprogramming processes.
Conclusions:
- Nuclear receptors are essential components of the molecular machinery controlling pluripotency.
- Further research into nuclear receptors will advance stem cell applications and understanding of cell fate.
- This review consolidates current knowledge and identifies future research avenues.
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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.
01:14Introduction 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...
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...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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.
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02:33Combinatorial Gene Control
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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...
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