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Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

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...
Methods of Nuclear Reprogramming01:24

Methods 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.
Chromatin Modification in iPS Cells01:32

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...
Combinatorial Gene Control02:33

Combinatorial 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...
Introduction to Nuclear Reprogramming01:14

Introduction 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...

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Related Experiment Video

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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
11:38

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

Published on: November 26, 2018

Identification of Oct4-activating compounds that enhance reprogramming efficiency.

Wendong Li1, E Tian, Zhao-Xia Chen

  • 1Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 6, 2012
PubMed
Summary
This summary is machine-generated.

A novel compound, Oct4-activating compound 1 (OAC1), significantly boosts induced pluripotent stem cell (iPSC) reprogramming efficiency and speed. This discovery accelerates the development of iPSC technology for broader applications.

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Area of Science:

  • Stem cell biology
  • Molecular and cellular biology
  • Biochemistry

Background:

  • Induced pluripotent stem cells (iPSCs) hold great therapeutic potential but face challenges in reprogramming efficiency and speed.
  • Octamer-binding transcription factor 4 (Oct4) is a crucial regulator for maintaining embryonic stem cell (ESC) pluripotency and is key to the reprogramming process.

Purpose of the Study:

  • To identify small molecules that can enhance the efficiency and speed of iPSC reprogramming.
  • To investigate the mechanism by which these molecules improve reprogramming.

Main Methods:

  • High-throughput screening of chemical libraries to identify compounds that activate Oct4.
  • Validation of compound activity using luciferase reporter genes for Oct4 and Nanog promoters.
  • Assessment of iPSC reprogramming efficiency and speed when compounds are added to the standard reprogramming factor cocktail (Oct4, Sox2, c-Myc, Klf4).
  • Characterization of derived iPSCs for morphology, gene expression, and developmental potential.

Main Results:

  • A compound, OAC1, was identified that activates both Oct4 and Nanog promoters.
  • OAC1 significantly enhanced iPSC reprogramming efficiency and accelerated the reprogramming process when used with the quartet factors.
  • Two structural analogs of OAC1 also demonstrated similar activating and enhancing effects.
  • The iPSCs generated using OAC1 exhibited typical ESC characteristics, including morphology, gene expression, and developmental potential.
  • OAC1's mechanism appears unique, independent of p53-p21 inhibition or Wnt-β-catenin activation, and involves increasing transcription of the Oct4-Nanog-Sox2 triad and Tet1.

Conclusions:

  • OAC1 and its analogs are effective small molecules for enhancing iPSC reprogramming.
  • These compounds offer a promising strategy to overcome current limitations in iPSC technology.
  • OAC1's novel mechanism provides new insights into the regulation of pluripotency and reprogramming.