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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...
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...
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...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
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T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications.

Frederic Lluis1, Luigi Ombrato, Elisa Pedone

  • 1Centre de Regulació Genòmica, Universitat Pompeu Fabra, 08003 Barcelona, Spain.

Proceedings of the National Academy of Sciences of the United States of America
|July 7, 2011
PubMed
Summary

Removing T-cell factor 3 (Tcf3) enhances somatic cell reprogramming into induced pluripotent stem cells. Tcf3 represses reprogramming potential by maintaining heterochromatin, and its absence facilitates epigenetic changes for pluripotency.

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Direct Lineage Reprogramming of Adult Mouse Fibroblast to Erythroid Progenitors
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Published on: December 14, 2018

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Published on: December 14, 2018

Area of Science:

  • Epigenetics
  • Stem Cell Biology
  • Cellular Reprogramming

Background:

  • Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) requires overcoming epigenetic barriers like heterochromatin.
  • T-cell factor 3 (Tcf3) is a known repressor of β-catenin target genes, potentially influencing cellular plasticity.

Purpose of the Study:

  • To investigate the role of T-cell factor 3 (Tcf3) in the efficiency of somatic cell reprogramming.
  • To determine the impact of Tcf3 absence on the epigenetic landscape during reprogramming.

Main Methods:

  • Utilizing Tcf3 knockout (Tcf3(-/-)) embryonic stem (ES) cells and neural precursor cells (NPCs).
  • Analyzing genome-wide histone modifications, specifically AcH3 and H3K9me3.
  • Assessing reprogramming efficiency via cell fusion and direct NPC reprogramming.

Main Results:

  • Absence of Tcf3 significantly and rapidly enhanced NPC reprogramming efficiency.
  • Tcf3(-/-) ES cells exhibited increased AcH3 and decreased H3K9me3 genome-wide, facilitating NPC reprogramming after fusion.
  • Tcf3 silencing during NPC reprogramming led to early increases in AcH3 and decreases in H3K9me3 heterochromatin foci.

Conclusions:

  • T-cell factor 3 (Tcf3) acts as a key repressor of the reprogramming potential in somatic cells.
  • Tcf3 regulates heterochromatin formation and epigenetic modifications crucial for achieving pluripotency.
  • Targeting Tcf3 offers a promising strategy to improve the efficiency of induced pluripotent stem cell generation.