Stem Cells in Regeneration and Aging

A process where two animals are surgically joined to share a circulatory system, enabling the exchange of blood and its components. This technique is useful for studying the effects of aging on stem cells and tissue regeneration.

Undifferentiated cells with the potential to develop into any type of cell in the body. They are crucial for tissue regeneration and repair.

The process of replacing or restoring lost or damaged tissue or organs. Some animals are much better at regeneration than others.

A type of flatworm with remarkable regenerative abilities, capable of regenerating a complete organism from a single cell.

The formation of new neurons in the brain, a process that continues throughout life in some organisms.

A cellular division where only one daughter cell inherits the fate determinant and becomes a stem cell, while the other daughter cell commits to differentiation.

A cellular division where both daughter cells inherit the fate determinant and remain stem cells.

The local environment that influences the fate of a stem cell, determining whether it differentiates or remains a stem cell.

The random or probabilistic nature of stem cell fate determination, where each daughter cell has an equal chance of differentiating or remaining a stem cell.

The gradual decline in the ability of stem cells to maintain their function and repopulate tissues with age.

The study of how internal factors (cell-autonomous) and external factors (environmental) contribute to changes in stem cell function during aging.

A young stem cell niche cannot rescue the function of old stem cells, suggesting that internal factors within the old stem cells play a role in aging.

An old stem cell niche can support the function of young stem cells, suggesting that environmental factors can influence stem cell function but don't cause aging.

Olfactory neurons, responsible for smell, are continuously replaced throughout life. This process ensures that the olfactory system remains sensitive to new scents.

In adult mice and humans, a small percentage (1.75% per year) of neurons in the hippocampus are replaced. The hippocampus is vital for learning and memory.

Some songbirds undergo dramatic neuronal turnover during breeding season. They lose and replace neurons in a process that refines their songs for attracting mates.

Neural stem cells are undifferentiated cells capable of becoming neurons or other brain cell types. These cells can be isolated, grown in culture, and then directed to differentiate into specific cell types.

Neural stem cells can be transplanted into an adult brain. Remarkably, they adapt to their new location and contribute to the existing circuitry. For example, hippocampal stem cells transplanted into the olfactory bulb integration pathway become functional olfactory neurons.

Neural stem cell transplantation has potential for treating nervous system damage caused by stroke, injuries, and diseases. However, clinical trials using this approach have yielded mixed results. Further research is ongoing to improve the effectiveness and safety of stem cell therapy.

Cultured embryonic stem cells (ES cells) can be genetically manipulated and then injected back into a developing blastocyst, potentially modifying the genetic makeup of the resulting organism.

ES-derived cells can differentiate into any cell type in the body, including germ cells, allowing the creation of mice with all cells inheriting genes from the original ES cell line.

The transcription factors Oct4, Sox2, Myc, and Klf4 (OSKM factors) induce their own synthesis, creating a self-sustaining loop that maintains cells in an ES cell-like state.

Forced expression of OSKM factors in fibroblasts can convert a small percentage into pluripotent stem cells (iPS cells), capable of being incorporated into a blastocyst to form a chimeric mouse.

A promoter active only in embryonic stem cells is used alongside a G418 resistance gene. This allows researchers to select for cells that have successfully converted to iPS cells.

While OSKM factors encourage reprogramming, many fibroblasts fail to downregulate somatic markers and activate pluripotency genes, resulting in unsuccessful conversion to iPS cells.

Several factors can enhance the efficiency of fibroblast to iPS cell conversion, particularly those that alter chromatin states, influencing gene expression.

Chromatin state modifications, including those affecting histone modifications and DNA methylation, play a critical role in enhancing iPS cell reprogramming efficiency.

Factors influencing chromatin structure, such as histone modifications and DNA methylation, can significantly affect the successful reprogramming of fibroblasts to iPS cells.

ES and iPS cells can be guided to develop into specific adult cell types and organoids in a laboratory setting. This process involves manipulating the environment and providing specific cues to guide their differentiation.

When introduced to a developing embryo or adult tissue, ES and iPS cells fail to receive the correct signals and develop properly. Instead, they can form a tumor called a teratoma, consisting of a confusing mix of different tissue types.

Embryoid bodies are three-dimensional cell clusters that resemble early embryos. They are formed by allowing cultured stem cells to aggregate together. The cells within these structures start to specialize.

By manipulating the culture conditions and adding specific factors, the cells within embryoid bodies can be directed to differentiate into various specialized cell types. This allows researchers to study and produce different types of cells.

ES and iPS cells can self-assemble into complex three-dimensional structures resembling organs. These structures, called organoids, allow researchers to study organ development and diseases in a controlled environment.

Human ES cells have been successfully used to create a three-dimensional eye-like structure called an optic cup. This organoid includes a developing retina with multiple layers of neural cells, similar to the one that forms during normal eye development in vivo.

iPS cells derived from an individual with a genetic disease can be used to study the disease mechanism and test potential drug therapies. By analyzing these cells, researchers can understand how the disease affects cell function and identify potential treatments.

The genetic defect in iPS cells can potentially be corrected, paving the way for cell-based therapy. Corrected iPS cells could be differentiated into specific cell types and transplanted back into the individual without the risk of immune rejection.