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Related Concept Videos

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program11:00

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This protocol describes how to study cellular processes during cell fate conversion in Caenorhabditis elegans in vivo. Using transgenic animals, allowing heat-shock promoter-driven overexpression of the neuron fate-inducing transcription factor CHE-1 and RNAi-mediated depletion of the chromatin-regulating factor LIN-53 germ cell to neuron reprogramming can be observed in vivo.
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Related Experiment Video

Updated: Jan 19, 2026

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
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Mitigating Antagonism between Transcription and Proliferation Allows Near-Deterministic Cellular Reprogramming.

Kimberley N Babos1, Kate E Galloway1, Kassandra Kisler2

  • 1Eli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Cell Stem Cell
|September 17, 2019
PubMed
Summary

Overcoming cellular reprogramming barriers requires balancing high transcription and DNA replication. A novel cocktail enables simultaneous hypertranscription and hyperproliferation, increasing reprogramming efficiency 100-fold.

Keywords:
Repsoxgenomic instabilityhypertranscriptionp53reprogrammingsingle-cell RNA-seqtopoisomerasetranscription factortranscription rate

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Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
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Related Experiment Videos

Last Updated: Jan 19, 2026

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
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Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
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Application of RNAi and Heat-shock-induced Transcription Factor Expression to Reprogram Germ Cells to Neurons in C. elegans
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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cellular reprogramming generates diverse cell types for therapies but is inefficient.
  • Epigenetic barriers limit successful lineage conversion.
  • Balancing transcription and DNA replication is crucial for reprogramming.

Purpose of the Study:

  • To investigate methods for overcoming epigenetic barriers in cellular reprogramming.
  • To identify factors that enhance the efficiency of somatic cell lineage conversion.
  • To understand the interplay between transcription, DNA replication, and reprogramming.

Main Methods:

  • Examined reprogramming of fibroblasts into motor neurons and other somatic cell types.
  • Utilized transcription factor overexpression to induce high transcription rates.
  • Identified and applied a chemical and genetic cocktail activating topoisomerases.
  • Assessed cell proliferation and lineage conversion rates.

Main Results:

  • Sustaining hypertranscription and transgene expression in hyperproliferative cells is critical.
  • Hypertranscription impedes DNA replication and cell proliferation.
  • A cocktail activating topoisomerases enables simultaneous hypertranscription and hyperproliferation.
  • Reprogramming rates increased 100-fold in treated cells.

Conclusions:

  • Relaxing biophysical constraints, specifically by enabling simultaneous hypertranscription and hyperproliferation, overcomes molecular barriers to cellular reprogramming.
  • This approach significantly enhances the efficiency of generating new cell types.
  • The findings have implications for disease modeling and regenerative medicine.