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

Multipotency and Niche of Bulge Stem Cell01:06

Multipotency and Niche of Bulge Stem Cell

3.8K
A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
3.8K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

5.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.0K

You might also read

Related Articles

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

Sort by
Same author

Large distant deletion disrupts CDKN2A enhancer and predisposes to melanoma.

medRxiv : the preprint server for health sciences·2026
Same author

Estimating the Sodium Content: A Case Series of Benign and Malignant Renal Tumours Using <sup>23</sup>Na-MRI at 3 T.

NMR in biomedicine·2026
Same author

Fibroblastic aspartoacylase suppresses TGFβ-mediated responses and cancer progression.

Nature communications·2026
Same author

GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma.

Cancer research·2026
Same author

Branching out takes anti-tumor immunity down a NOTCH.

Nature immunology·2026
Same author

Cardiolipin preserves T<sub>reg</sub> metabolic fitness and immune homeostasis in the gut.

Nature metabolism·2026

Related Experiment Video

Updated: Aug 24, 2025

Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci
09:07

Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci

Published on: March 4, 2021

3.0K

HIRA loss transforms FH-deficient cells.

Lorea Valcarcel-Jimenez1,2, Connor Rogerson1, Cissy Yong1,3,4

  • 1MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK.

Science Advances
|October 21, 2022
PubMed
Summary
This summary is machine-generated.

Loss of fumarate hydratase (FH) causes aggressive kidney cancer. Ablating histone cell cycle regulator (HIRA) promotes FH-deficient cell proliferation and invasion, revealing a new therapeutic target for hereditary leiomyomatosis and renal cell carcinoma.

More Related Videos

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.9K
Author Spotlight: Identification and Isolation of Quiescent Leukemia Stem Cells from Zebrafish T-ALL
06:41

Author Spotlight: Identification and Isolation of Quiescent Leukemia Stem Cells from Zebrafish T-ALL

Published on: July 19, 2024

925

Related Experiment Videos

Last Updated: Aug 24, 2025

Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci
09:07

Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci

Published on: March 4, 2021

3.0K
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.9K
Author Spotlight: Identification and Isolation of Quiescent Leukemia Stem Cells from Zebrafish T-ALL
06:41

Author Spotlight: Identification and Isolation of Quiescent Leukemia Stem Cells from Zebrafish T-ALL

Published on: July 19, 2024

925

Area of Science:

  • Cellular biology
  • Cancer research
  • Biochemistry

Background:

  • Fumarate hydratase (FH) is a mitochondrial enzyme crucial for the tricarboxylic acid (TCA) cycle.
  • Germline mutations in FH cause hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a syndrome linked to aggressive kidney cancer.
  • FH-deficient cells in mice develop kidney cysts, not carcinomas, indicating tumor-suppressive mechanisms that are not fully understood.

Purpose of the Study:

  • To identify genes that, when lost, promote the proliferation of FH-deficient cells.
  • To understand the mechanisms by which FH-deficient cells overcome tumor suppression.
  • To uncover potential therapeutic targets for HLRCC.

Main Methods:

  • Genome-wide CRISPR-Cas9 screening was employed to identify genes essential for the proliferation of FH-deficient cells.
  • In vitro and in vivo assays were used to assess the impact of gene ablation on cell proliferation and invasion.
  • Molecular analyses were performed to investigate the mechanistic link between gene loss, MYC activation, and nucleotide metabolism.

Main Results:

  • Depletion of the histone cell cycle regulator (HIRA) significantly enhances the proliferation and invasion of FH-deficient cells.
  • Loss of HIRA activates MYC and its target genes, leading to increased nucleotide metabolism in FH-deficient cells.
  • This effect is independent of HIRA's canonical histone chaperone activity.

Conclusions:

  • HIRA acts as a critical suppressor of proliferation and invasion in FH-deficient cells.
  • The loss of HIRA promotes HLRCC tumorigenesis by activating MYC-driven nucleotide metabolism.
  • Targeting HIRA or MYC pathway could be a potential therapeutic strategy for HLRCC patients.