Related Experiment Video
Updated: Jan 3, 2026
11:24
Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
11.4K
Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells
Annika Scheffold1, Ali H Baig2, Zhiyang Chen2
1Department of Internal Medicine III, University Hospital Ulm, 89081, Ulm, Germany.
Leukemia
|November 16, 2019
Summary
Aging hematopoietic stem cells develop resistance to DNA damage, linked to Hedgehog pathway activation. Inhibiting this pathway may prevent age-related blood disorders.
Area of Science:
- Hematology
- Molecular Biology
- Aging Research
Background:
- Aging hematopoietic system shows DNA damage accumulation and myeloid-skewed differentiation.
- Mechanisms underlying these aging-related changes in blood cells are not fully understood.
Purpose of the Study:
- To investigate the role of DNA damage resistance in aging hematopoietic progenitor cells.
- To identify molecular pathways associated with aging-related myeloid skewing and DNA damage tolerance.
Main Methods:
- Analysis of DNA damage resistance in aged versus young hematopoietic progenitor cells.
- Investigation of Hedgehog (Hh) pathway activity in hematopoietic progenitors.
- Manipulation of Hh signaling in hematopoietic progenitor cells to assess effects on DNA damage response and proliferation.
Main Results:
- Aging hematopoietic progenitor cells, especially myeloid progenitors, display increased resistance to bulky DNA lesions.
- Aging-associated activation of the Hedgehog (Hh) pathway correlates with enhanced DNA damage tolerance.
- Inhibition of Hh signaling in aged progenitors restored normal DNA damage responses and proliferation.
- Activation of Hh signaling in young progenitors mimicked aging-related impaired DNA damage responses.
Conclusions:
- Increased Hedgehog (Hh) pathway activity in aging contributes to DNA damage tolerance and myeloid-skewed differentiation.
- Modulating Hh activity presents a potential therapeutic strategy for age-related hematopoietic disorders.
Related Concept Videos
02:33Hedgehog Signaling Pathway
9.7K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.7K
01:01Regulation of Hematopoietic Stem Cells
3.8K
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...
3.8K
02:36DNA Damage can Stall the Cell Cycle
9.9K
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...
9.9K
02:36DNA Damage Can Stall the Cell Cycle
3.0K
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...
3.0K
01:19Multipotency of Hematopoietic Stem Cells
3.7K
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...
3.7K
02:23Abnormal Proliferation
5.0K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K