Lecture 3: iPS Cells

Induced pluripotent stem cells are generated from adult cells and are capable of giving rise to various cell types in the body. This process of reprogramming adult cells back into a pluripotent state was pioneered by Shinya Yamanaka.

With iPS cells, researchers can create an unlimited supply of specific cell types without the need for embryonic tissues. This allows for the development of disease models, drug screening, and potential therapeutic applications.

The four Yamanaka factors (OCT3/4, SOX2, KLF4, and c-MYC) are essential transcription factors that can reprogram differentiated cells back into a pluripotent state. These factors act like switches that turn on specific genes responsible for pluripotency.

Reprogramming methods involve introducing the Yamanaka factors into adult cells using various techniques. These methods aim to efficiently and safely reprogram cells back to a pluripotent state.

During development, cells transition from a totipotent state to a pluripotent state and then to more specialized states. This differentiation process involves epigenetic changes, which are alterations in gene expression without changing the underlying DNA sequence.

iPS cells can be used to create in vitro disease models, allowing researchers to study the disease process in detail and develop targeted drug therapies.

iPS cells can be genetically modified to repair faulty genes, potentially leading to the development of new therapies for genetic disorders.

The process by which cells become specialized with distinct functions, involving selective activation or inactivation of specific genes.

Changes in gene expression without alterations in DNA sequence, including DNA methylation and histone modifications.

A chemical modification of DNA, mainly by adding a methyl group (CH3), which can affect gene expression.

Proteins that bind to DNA and regulate gene expression by promoting or inhibiting transcription.

A process that modifies the structure of chromatin, the complex of DNA and associated proteins, influencing gene accessibility.

The fundamental protein units of chromatin, around which DNA wraps.

A transcription factor crucial for maintaining pluripotency, the ability of a cell to develop into any cell type.

Cells with the ability to differentiate into any cell type in the body.

The ability of a cell to develop into any cell type in the body.

A transcription factor that promotes gene expression to maintain an undifferentiated, pluripotent state.

A histone modification associated with actively transcribed genes, indicating an open chromatin state.

A histone modification often associated with repressed genes and tightly packed chromatin.

A key epigenetic modification associated with long-term gene silencing. It prevents transcription factor binding and compacts chromatin.

The process of reversing epigenetic modifications to restore a cell to a pluripotent state, like an embryonic stem cell.

During reprogramming, the four Yamanaka factors work together to remodel chromatin, leading to changes in gene expression.

The early phase of reprogramming involves changes in gene expression, cell shape, and metabolism.

The late phase of reprogramming involves activation of pluripotency genes, repression of tissue-specific genes, and further chromatin remodeling.

Reprogramming into iPS cells is possible in a variety of species, suggesting a universal mechanism.

iPSCs are generated from adult cells and can differentiate into different cell types, but they retain epigenetic memories of their origin which can bias their differentiation.

ESCs are derived from the pre-implantation blastocyst and exhibit naive pluripotency, capable of forming both embryonic and extraembryonic tissues.

EpiSCs are derived from the post-implantation epiblast and are primed for specific developmental pathways, with limited extraembryonic potential.

ESCs require specific signals for differentiation, while EpiSCs respond to a broader range of cues and are more prone to spontaneous differentiation.

Differences in PSCs may explain why differentiation to certain cell types remains elusive.

A phase during iPSC reprogramming characterized by random and variable changes with uncertain outcomes. It involves down-regulation of lineage-specific genes and commencement of mesenchymal-epithelial transition. This phase is marked by uncertainty and a dynamic shift towards pluripotency.

A phase during iPSC reprogramming characterized by predictable and orderly progression towards a stable pluripotent state. This phase involves bivalent methylation of H3K4m33/H3K27me3 on promoter regions, sequential activation of pluripotency genes, and a flat, round cell morphology.

A method of assessing iPSC pluripotency that involves transplanting iPSCs into a host organism and observing their ability to differentiate into all three germ layers (endoderm, mesoderm, and ectoderm). The resulting tumor is called a teratoma.

A method of assessing iPSC pluripotency that involves injecting iPSCs into blastocysts (early-stage embryos). The iPSCs contribute to the development of the embryo and eventually give rise to different tissues in the chimeric animal.

The process of converting a differentiated cell (e.g., skin cell) back into a pluripotent state. This is achieved by introducing specific transcription factors, such as the Yamanaka factors, into the cell.

The state of a cell that has not yet differentiated into a specialized cell. These cells are characterized by the ability to self-renew and differentiate into any cell type in the body.