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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...
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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...
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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...
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Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
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Chromatin Modification in iPS Cells01:32

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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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Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
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Reprogramming cells with synthetic proteins.

Xiaoxiao Yang, Vikas Malik, Ralf Jauch1

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Summary
This summary is machine-generated.

Cellular reprogramming using transcription factors (TFs) shows cell fates are plastic. Protein engineering of TFs enhances reprogramming for regenerative medicine, addressing clinical needs for functional cells.

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Area of Science:

  • Cellular and Molecular Biology
  • Regenerative Medicine
  • Biotechnology

Background:

  • Cellular differentiation is not a fixed process, as demonstrated by the conversion of cell types using transcription factors (TFs).
  • Transcription factors possess the ability to access and modify chromatin, thereby influencing gene expression programs.
  • Cellular reprogramming holds promise for disease modeling, drug testing, and developing cell-based therapies for degenerative diseases.

Purpose of the Study:

  • To highlight the unmet clinical need for producing sufficient quantities of fully functional, in vivo-like terminally differentiated cells.
  • To emphasize the optimization of transcription factors (TFs) through protein engineering as a key strategy to enhance cellular reprogramming.
  • To explore how protein design approaches can overcome current limitations in reprogramming technologies for clinical applications.

Main Methods:

  • Utilizing defined TF cocktails to induce cell fate conversion.
  • Employing protein engineering strategies to optimize TFs, including creating chimeric TFs and designer transcription activator-like effectors.
  • Focusing engineering efforts on specific TFs such as Oct4, MyoD, Sox17, Nanog, and Mef2c.

Main Results:

  • Demonstrated that cell fates are malleable and can be altered through TF expression.
  • Showcased the potential of TFs to reprogram cells by accessing and altering genetic regulatory information and chromatin structure.
  • Identified protein engineering as a viable strategy to improve TF function for enhanced reprogramming outcomes.

Conclusions:

  • Protein engineering of transcription factors is crucial for advancing regenerative medicine by producing safer and more effective cells.
  • Overcoming current hurdles in cell reprogramming requires the comprehensive application of protein design principles.
  • Optimized TF-driven reprogramming could pave the way for the clinical use of reprogrammed cells in treating degenerative diseases.