Related Experiment Video
Updated: Aug 3, 2025
11:06
Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
13.1K
Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage
Pradeep Ramalingam1, Michael C Gutkin2, Michael G Poulos1
1Department of Medicine, University of Florida Health Cancer Center, Gainesville, FL, USA.
Nature Communications
|April 10, 2023
Summary
Restoring aged bone marrow niches with Netrin-1 rejuvenates blood stem cells. This study reveals Netrin-1
Area of Science:
- Stem Cell Biology
- Gerontology
- Hematology
Background:
- Aging impairs stem cell function due to defects in their supportive niches.
- Mechanisms of age-related niche dysfunction and potential for rejuvenation are not fully understood.
Purpose of the Study:
- To investigate if rejuvenating bone marrow (BM) niches can restore aged blood stem cell function.
- To identify key regulators of BM niche aging.
Main Methods:
- Niche-specific gene deletion of Netrin-1 in mice.
- Supplementation of aged mice with Netrin-1.
- Assessing blood stem cell fitness and BM microenvironment.
- Analyzing DNA damage responses (DDR).
Main Results:
- Netrin-1 is identified as a critical regulator of BM niche aging.
- Loss of Netrin-1 accelerates BM microenvironment aging.
- Netrin-1 supplementation rejuvenates aged niche cells and restores aged blood stem cell fitness.
- Netrin-1 is essential for active DNA damage responses; its decline causes DNA damage accumulation in the BM.
- Netrin-1 resolves DNA damage and restores regenerative potential of aged BM niches and stem cells.
Conclusions:
- Netrin-1 is crucial for maintaining BM niche health and blood stem cell function during aging.
- Netrin-1 supplementation can reverse age-related stem cell defects and enhance resilience to chemotherapy.
- Targeting Netrin-1 offers a potential therapeutic strategy for age-related stem cell decline.
More Related Videos
10:03Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging
Published on: August 1, 2017
11.8K
11:06Combining Intravital Fluorescent Microscopy IVFM with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
Published on: March 21, 2017
8.0K
Related Concept Videos
01:26Stem Cell Niche
5.2K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
5.2K
01:19Multipotency of Hematopoietic Stem Cells
3.2K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.2K
02:37DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
01:21Stem Cell Therapy for Tissue Regeneration
4.1K
Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
4.1K
01:01Regulation of Hematopoietic Stem Cells
3.3K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.3K
02:25Overview of DNA Repair
31.2K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.2K