Stem cells are the foundational cells of the body, characterized by their capacity for self-renewal and their ability to mature into more specialized cell types. This unique dual capability makes them a subject of intense scientific interest. The terminology used to describe their potential often causes confusion, specifically the difference between a totipotent cell and a pluripotent cell. This article clarifies the precise scientific classification of embryonic stem cells by detailing the spectrum of cell potency and explaining the biological origin that determines their potential.
Understanding the Hierarchy of Stem Cell Potential
The potential of a stem cell to differentiate, or specialize, is described by its potency, which exists on a spectrum defined by four main stages. At the highest end is totipotency, describing a cell capable of forming every cell type in the body, including extra-embryonic tissues like the placenta and umbilical cord. The fertilized egg, or zygote, and the cells resulting from the first few divisions are the only naturally occurring totipotent cells in mammals.
The next step down is pluripotency, where cells retain the ability to generate all cell types that make up the organism itself, but they can no longer form the placenta or other supporting structures. These cells generate derivatives of all three primary germ layers—the ectoderm, mesoderm, and endoderm—which ultimately form the entire body.
The third level, multipotency, is a more restricted capability, limiting the cell to differentiating into a finite range of cell types within a specific tissue or organ system. For instance, hematopoietic stem cells in bone marrow are multipotent as they produce various blood cells, such as red blood cells and different white blood cells.
The most specialized form is unipotency, where a stem cell can only differentiate into one cell type, although it retains the ability to self-renew. This hierarchical system illustrates a natural progression in development: as cells divide and specialize, their developmental potential becomes progressively limited.
The Definitive Classification of Embryonic Stem Cells
Embryonic Stem Cells (ESCs) are classified as pluripotent because of the specific stage of embryo development from which they are derived. ESCs are isolated from the inner cell mass (ICM) of the blastocyst, a structure that forms approximately four to seven days after fertilization. The blastocyst is a hollow sphere of cells, and the ICM is a small cluster of cells tucked inside.
By the time the blastocyst forms, a crucial cell fate decision has separated the cells that will form the fetus from the cells that will form the placenta. The outer layer, known as the trophectoderm, is already committed to forming the extra-embryonic tissues. Because ESCs are taken only from the ICM, they have lost the ability to develop into the trophectoderm and cannot form a complete organism with a placenta.
While ESCs can successfully differentiate into any of the over 200 cell types found in the developed body, they cannot re-create the whole organism. The ability to generate all cell types of the organism is the precise definition of pluripotency, confirming why the ICM-derived cells are not totipotent.
The Research Value of Pluripotency
The potential of pluripotent stem cells holds significant value for medical research and biotechnology. Because they can be maintained in the laboratory and directed to become virtually any cell type, scientists utilize them to generate large quantities of specialized cells for study. This capacity allows researchers to create human cell models of diseases that would otherwise be impossible to study in a living patient.
A primary application involves generating specific cell types, such as heart muscle cells (cardiomyocytes) or brain cells (neurons), for use in high-throughput drug testing. This process allows pharmaceutical companies to screen thousands of compounds for efficacy and toxicity on human cells before moving to clinical trials. Screening on human cells provides a more human-relevant prediction of drug response.
The ability to differentiate ESCs into various lineages also facilitates the creation of three-dimensional tissue structures called organoids, or “mini-organs.” These microscopic, self-organizing structures mimic the architecture and function of native human organs. Organoids derived from pluripotent stem cells serve as sophisticated models for understanding complex processes, like early human development, or for modeling diseases.