P19 cells are a line of pluripotent stem cells derived from mice, frequently used in laboratories to study how cells specialize. As a model system for understanding developmental processes, their ability to be guided into different cell types allows researchers to observe cellular specialization in a controlled setting. It is important to distinguish the P19 cell line from the p19 protein (p19ARF), a tumor suppressor involved in cellular regulation. The shared name is coincidental, and the two have entirely different functions within biology.
Origin and Key Characteristics
The P19 cell line was established in 1982 from an experimentally induced teratocarcinoma in a mouse. A teratocarcinoma is a tumor that contains a mixture of undifferentiated stem cells and various differentiated cell types. Researchers induced this tumor by transplanting a 7.5-day-old mouse embryo into the testis of a mouse, from which the P19 cell line was isolated. These cells are easy to maintain and grow rapidly without the need for feeder cells, which are often required to support other stem cell types.
The defining characteristic of P19 cells is their pluripotency. This means a single P19 cell has the capacity to differentiate into cell types from all three primary germ layers of an embryo: the ectoderm, endoderm, and mesoderm. When these cells were injected into the blastocysts of a different mouse strain, they contributed to the development of tissues from all three layers, confirming their pluripotent nature.
The Process of Differentiation
The differentiation of P19 cells can be directed into specific lineages using chemical inducers. This process involves encouraging the cells to form aggregates, which mimics the multi-cellular environment of an early embryo. When these aggregates are exposed to certain chemicals, they reliably transform into predictable cell types.
The most common method involves using retinoic acid (RA) to guide the cells toward a neural fate. Treatment with RA induces P19 cells to differentiate into neurons and glial cells, such as astrocytes, which are the main cell types of the nervous system. This provides a consistent system for studying the events that govern the formation of the nervous system.
In contrast, exposing P19 cell aggregates to dimethyl sulfoxide (DMSO) pushes them down a different developmental pathway. Treatment with 0.5% to 1.0% DMSO causes the cells to differentiate into cardiac and skeletal muscle tissues. If cells are exposed to both RA and DMSO, they follow the neural differentiation pathway dictated by retinoic acid.
Applications in Scientific Research
The ability to control the differentiation of P19 cells makes them useful for various research applications. One use is as a model system for neurogenesis, the process of forming new neurons. Scientists can observe the stages of neural development in a laboratory dish, helping to uncover the genetic and molecular signals that guide the formation of the brain and nervous system.
This controlled environment is also useful in developmental toxicology and drug discovery. Researchers can expose differentiating P19 cells to chemicals or drugs to assess their effects. For example, scientists can test whether a new compound disrupts the normal formation of neurons or muscle cells, providing early indications of potential toxicity or therapeutic effects.
These cells are also amenable to genetic modification, allowing for more detailed investigations. Scientists can introduce or remove specific genes to study their roles in the signaling pathways that control muscle or nerve cell development.
Comparison to Other Stem Cells
P19 cells are distinct from other stem cells, particularly embryonic stem cells (ESCs). The primary distinction lies in their origin. P19 cells are classified as embryonal carcinoma cells because they are derived from a teratocarcinoma, a type of tumor. In contrast, ESCs are derived directly from the inner cell mass of a blastocyst, an early-stage embryo.
This difference in origin carries both practical and ethical implications. The use of tumor-derived P19 cells generally avoids the ethical controversies associated with the destruction of viable embryos required to establish ESC lines. Biologically, while both cell types are pluripotent, they often exhibit different efficiencies and require distinct protocols for differentiation.
The choice between using P19 cells and ESCs often depends on the specific research question. For experiments focused on the fundamental mechanisms of neural or muscle differentiation, the reliability and ease of use of P19 cells make them a suitable choice.