Cell fate conversion by conditionally switching the signal-transducing domain of signalobodies

Yuichiro Tone1, Masahiro Kawahara, Jun Hayashi

  • 1Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Insights

This study introduces a novel cell fate control system using signalobodies and Cre/loxP recombination. It enables precise control over cell growth and death, crucial for advanced cell therapies.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cell Biology

Background:

  • Precise control of cell fates is essential for biomedical applications like cell therapies.
  • Existing methods for regulating cell signaling often suffer from leakiness and complexity.

Purpose of the Study:

  • To develop a novel, highly controllable cell fate conversion system.
  • To improve upon existing techniques for regulating cell signaling and fate.

Main Methods:

  • Utilized antibody/receptor chimeras called "signalobodies".
  • Developed a "switch vector" incorporating signalobody genes flanked by loxP sites.
  • Combined the switch vector with a Cre/loxP recombination system for conditional gene expression.

Main Results:

  • Cells transduced with the switch vector exhibited enhanced growth in the presence of a specific antigen.
  • Cre expression triggered the activation of a death signalobody, leading to conditional cell death.
  • Demonstrated a system with reduced leakiness and complexity compared to previous methods.

Conclusions:

  • The developed signalobody and Cre/loxP system offers precise, conditional control over cell fates.
  • This technology has potential applications in cell therapies, differentiation, and migration control.
  • The system's modular design allows for adaptation to various signal-transducing domains for diverse cell fate conversions.

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Forced Transdifferentiation01:28

Forced Transdifferentiation

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.
Artificial transdifferentiation occurs...