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Related Concept Videos

CRISPR01:59

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...
CRISPR and crRNAs02:53

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
CRISPR01:59

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
CRISPR/Cas9 Genome Editing01:28

CRISPR/Cas9 Genome Editing

The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...

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Related Experiment Video

Updated: May 8, 2026

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity
07:52

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity

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In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution.

Peter F Renz1, Umesh Ghoshdastider1, Simona Baghai Sain2

  • 1Institute for Regenerative Medicine (IREM), University of Zurich, Schlieren-Zurich, Switzerland.

Nature
|July 17, 2024
PubMed
Summary
This summary is machine-generated.

This study reveals distinct tumor necrosis factor (TNF) signaling programs during cancer evolution. A novel in vivo CRISPR screen identifies TNF signaling as a driver of clonal expansion and invasion in squamous cell carcinoma.

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Area of Science:

  • Cancer Biology
  • Genetics
  • Immunology

Background:

  • Tumorigenesis involves clonal expansions driven by mutations, but mechanisms leading to malignant transformation remain unclear.
  • Understanding clonal dynamics in normal tissues is crucial for deciphering early cancer development.

Purpose of the Study:

  • To systematically investigate tissue-wide clonal dynamics and gene programs during tumor evolution using in vivo single-cell CRISPR.
  • To uncover mechanisms driving clonal expansions and malignant transformation in squamous cell carcinoma.

Main Methods:

  • Developed an in vivo single-cell CRISPR strategy coupled with ultrasound-guided in utero lentiviral microinjections.
  • Utilized longitudinal monitoring via single-cell RNA sequencing and guide capture to analyze clonal expansions.
  • Investigated the role of 150 frequently mutated squamous cell carcinoma genes.

Main Results:

  • Identified a tumor necrosis factor (TNF) signaling module, involving TNF receptor 1 and macrophages, as a driver of clonal expansions in epithelial tissues.
  • Observed downregulation of the TNF signaling module during tumorigenesis, with a switch to an autocrine TNF program in invasive cancer cells.
  • Demonstrated that the autocrine TNF program mediates invasive properties and correlates with shorter patient survival.

Conclusions:

  • In vivo single-cell CRISPR screening is a powerful tool for studying mammalian tissue dynamics.
  • Distinct TNF signaling programs play critical roles in tumor evolution, clonal expansion, and invasion.
  • Understanding the interplay between clonal expansion and tumorigenesis is vital for cancer research.