Related Experiment Video
Updated: Jun 16, 2026
09:41
Preparation of Single-Cell Suspension of Mouse Thymic Epithelial Cells and Staining of Intracellular Molecules for Flow Cytometric Analysis
Published on: July 26, 2024
Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution
Liguang Sun1, Jianfei Guo, Robert Brown
1Department of Biomedical Research, University of Texas Health Science Center at Tyler, 75708, USA.
Aging Cell
|February 17, 2010
Summary
The decline of the FoxN1 gene in thymic epithelial cells (TECs) accelerates aging of the thymus. Restoring FoxN1 levels partially reverses thymic aging and improves T-cell function in aged mice.
Area of Science:
- Immunology
- Developmental Biology
- Aging Research
Background:
- Age-related thymic involution, a decline in thymus function with age, is linked to gene expression changes in thymic epithelial cells (TECs).
- The specific role of the epithelial cell-autonomous gene FoxN1 in this process has been unclear due to limited functional studies.
Purpose of the Study:
- To investigate the impact of gradual FoxN1 gene loss on thymic aging.
- To determine if exogenous FoxN1 can rescue age-related thymic dysfunction.
Main Methods:
- Utilized a novel loxP-floxed-FoxN1(fx) mouse model with a ubiquitous CreER(T) (uCreER(T)) transgene for age-dependent, gradual FoxN1 deletion.
- Administered exogenous FoxN1-cDNA to aged wild-type mice to assess rescue effects.
Main Results:
- Mice with gradual FoxN1 deletion (uCreER(T)-fx/fx) exhibited accelerated thymic involution and TEC loss, with aging phenotypes appearing as early as 3-6 months.
- These accelerated aging phenotypes mimicked those of naturally aged mice (18-22 months).
- Intrathymic delivery of FoxN1-cDNA partially rescued thymic involution and improved peripheral CD4(+) T-cell function in aged mice.
Conclusions:
- A decrease in FoxN1 levels in TECs with age is a primary driver of thymic microenvironment deterioration.
- This decline in FoxN1 function contributes significantly to age-related thymic involution and impaired T-cell immunity.
Related Concept Videos
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
01:12Loss of Tumor Suppressor Gene Functions
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...
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...
01:12Loss of Tumor Suppressor Gene Functions
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...
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...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:19The Effect of Aging on Tissues
Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...