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Related Concept Videos

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Hybridoma Technology

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Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Scalable High Throughput Selection From Phage-displayed Synthetic Antibody Libraries
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Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries.

Joel W Blanchard1, Jia Xie2, Nadja El-Mecharrafie1

  • 1Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.

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|September 12, 2017
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Summary

Researchers discovered antibodies that trigger cell reprogramming at the cell surface, bypassing traditional nuclear factors. This opens new avenues for generating induced pluripotent stem cells (iPSCs) and understanding cell fate.

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Area of Science:

  • Cell Biology
  • Stem Cell Research
  • Immunology

Background:

  • Cellular reprogramming to induced pluripotent stem cells (iPSCs) typically involves nuclear transcription factors.
  • Developmental differentiation is initiated by membrane-bound signaling pathways.
  • Novel methods are needed to control cell fate and pluripotency.

Purpose of the Study:

  • To identify cell-surface-acting antibodies capable of inducing cellular de-differentiation and nuclear reprogramming.
  • To discover novel membrane-to-nucleus signaling pathways regulating pluripotency.
  • To establish antibody library screening as a method for discovering new biologics.

Main Methods:

  • Screening a large library of single-chain antibodies for reprogramming activity.
  • Identifying antibodies that replace key transcription factors like Sox2, Myc (c-Myc), and Oct4.
  • Investigating the molecular mechanism of antibody-mediated reprogramming, including protein-protein interactions.

Main Results:

  • Identified antibodies that can replace Sox2 or Oct4 in reprogramming mouse embryonic fibroblasts into iPSCs.
  • Discovered a Sox2-replacing antibody that antagonizes Basp1, de-repressing nuclear factors (WT1, Esrrb, Lin28a) independently of Sox2.
  • Developed three distinct methods for generating iPSCs by manipulating this pathway.

Conclusions:

  • Unbiased screening of antibody libraries is a powerful approach for discovering novel biologics and signaling pathways.
  • Cell-surface interactions can directly trigger nuclear reprogramming and regulate cell fate.
  • This study reveals new membrane-to-nucleus signaling mechanisms controlling pluripotency.