Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.

bioRxiv : the preprint server for biology·2026
Same author

Defining the heterogeneous molecular landscape of lung cancer cell responses to epigenetic inhibition.

Communications biology·2026
Same author

An expanded role for single-cell chemical genomics profiling in drug discovery.

The Biochemical journal·2026
Same author

Pervanadate: So much more than a protein tyrosine phosphatase inhibitor.

Science signaling·2026
Same author

Mapping kinase-dependent tumor immune adaptation with multiplexed single-cell CRISPR screens.

bioRxiv : the preprint server for biology·2026
Same author

Profiling tyrosine kinase substrate recognition using bacterial peptide display and deep sequencing.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: May 24, 2026

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants.

Anne E van Vlimmeren1,2, Ross M Giglio3,4, Ziyuan Jiang1

  • 1Department of Chemistry, Columbia University, New York, NY 10027, USA.

Science Advances
|May 22, 2026
PubMed
Summary

Diverse PTPN11 mutations alter protein tyrosine phosphatase SHP2 function, impacting Ras/MAPK signaling in developmental disorders and cancer. Different mutations can cause similar or distinct cellular outcomes, complicating disease understanding.

More Related Videos

Multiplexed Single Cell mRNA Sequencing Analysis of Mouse Embryonic Cells
08:30

Multiplexed Single Cell mRNA Sequencing Analysis of Mouse Embryonic Cells

Published on: January 7, 2020

Related Experiment Videos

Last Updated: May 24, 2026

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

Multiplexed Single Cell mRNA Sequencing Analysis of Mouse Embryonic Cells
08:30

Multiplexed Single Cell mRNA Sequencing Analysis of Mouse Embryonic Cells

Published on: January 7, 2020

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Protein tyrosine phosphatase SHP2 (encoded by PTPN11) regulates Ras/MAPK signaling downstream of receptor tyrosine kinases.
  • PTPN11 mutations are linked to developmental disorders like Noonan syndrome and various cancers.

Purpose of the Study:

  • To elucidate how diverse PTPN11 mutations dysregulate SHP2 signaling, impacting cellular outcomes and disease.
  • To correlate structural changes from mutations with functional and transcriptional consequences.

Main Methods:

  • Single-cell transcriptional profiling of cells expressing SHP2 variants.
  • Protein biochemistry and structural analysis.
  • Cell biology assays.

Main Results:

  • Loss of SHP2 catalytic activity does not fully replicate SHP2 knockout gene expression profiles.
  • Mechanistically distinct mutations can lead to convergent phenotypic effects.
  • Varied mutations at the same residue can result in divergent cellular states.

Conclusions:

  • Pathogenic PTPN11 mutations dysregulate SHP2 signaling through diverse mechanisms, leading to complex cellular outcomes.
  • Understanding the link between SHP2 structural changes, cellular responses, and disease is crucial.
  • This study provides a framework for interpreting the pathogenicity of different SHP2 variants.