Stem cells are the body’s raw materials, unspecialized cells that can develop into many different cell types. This ability allows them to serve as an internal repair system, dividing to replenish other cells as long as a person is alive. While much attention is given to their potential to differentiate, their shape is an often-overlooked characteristic. The morphology of a stem cell is not a random feature but a regulated aspect of its biology. The physical form a stem cell takes provides clues about its identity, intentions, and interactions with its environment.
The Functional Importance of Stem Cell Shape
A stem cell’s shape is linked to its function and behavior, acting as a direct reflection of its internal state and its communication with its surroundings. Changes in morphology can signal whether a cell is preparing to divide, migrating to a new location, or beginning specialization. A flattened and spread-out shape, for instance, might suggest a cell is firmly anchored, while a rounded shape could indicate it is in a less committed state or preparing for division.
The shape also dictates how a stem cell interacts with neighboring cells and the non-cellular environment known as the extracellular matrix. These physical interactions generate mechanical forces and tensions that the cell can sense. The shape is not merely a byproduct of cellular processes but an active participant in a feedback loop that governs the cell’s life. For example, the alignment and elongation of human embryonic stem cells can be influenced by the surfaces they grow on. The shape allows the cell to interpret signals from its microenvironment, including growth factors, cell-to-cell contacts, and physical forces.
Factors Governing Stem Cell Morphology
A stem cell’s shape is determined by a combination of internal structural components and external physical cues. Internally, the primary driver is the cytoskeleton, a dynamic network of protein filaments. This network includes actin filaments, which generate the forces for a cell to change shape and move, and microtubules, which provide structural support. The interplay between these cytoskeletal elements allows a cell to adopt and alter its morphology in response to various signals.
The cell’s external environment, the stem cell niche, also exerts a strong influence on its shape. This niche includes the extracellular matrix (ECM), a meshwork of proteins and carbohydrates that surrounds the cells. The composition and stiffness of the ECM provide physical anchors and generate mechanical forces. Other physical forces include shear stress from fluid flow, tension from adjacent tissues, and compression. For example, mechanical compression can promote a rounded cell shape in bone marrow-derived mesenchymal stem cells. Interactions with neighboring cells through adhesion molecules also constrain and define a cell’s shape.
Characteristic Stem Cell Shapes and Their Significance
Stem cells exhibit characteristic shapes that correlate with their type and functional state. A common morphology for pluripotent stem cells, like those grown in suspension, is a simple rounded or spherical shape. This compact form is associated with a naive or undifferentiated state, where the cell maintains its potential to become any cell type. Maintaining this rounded shape is also a requirement for some adult stem cells to differentiate into a cartilage-producing phenotype.
In contrast, many adult stem cells, such as mesenchymal stem cells (MSCs), display a spindle-shaped appearance when grown on a flat surface. This elongated shape is characteristic of cells that are actively migrating, proliferating, or beginning to commit to a specific lineage. This morphology is associated with strong adhesion to the underlying substrate, and the change from a rounded to a spindle shape alters the organization of the cell’s internal actin cytoskeleton.
Other stem cells may adopt more complex geometries depending on their location and function. Neural stem cells, for instance, can exhibit a stellate or branched shape as they integrate into the nervous system. This intricate morphology allows for the formation of numerous connections with other cells. The alignment and elongation of these cells can be guided by nanoscale patterns on the surfaces they grow on.
How Shape Directs Stem Cell Differentiation
A stem cell’s shape is not just a passive indicator of its state; it actively directs its differentiation pathway. The process by which physical cues like shape are converted into biochemical signals is known as mechanotransduction. This conversion can alter gene expression and guide a stem cell toward a specific fate. The shape of a cell determines the tension on its internal cytoskeleton, and this tension can trigger signaling cascades that influence which genes are turned on or off.
Forcing stem cells into specific shapes using micropatterning technologies has demonstrated this principle. When human adipose-derived stem cells are grown on geometric patterns, their differentiation changes based on their resulting shape. Cells that are allowed to become large and spread out tend to proliferate, while those constrained into smaller, more elongated shapes are more likely to differentiate.
The stiffness of the surface on which a stem cell grows can also direct its lineage. Mesenchymal stem cells cultured on soft substrates that mimic brain tissue are more likely to differentiate into neuron-like cells. When cultured on stiffer surfaces similar to muscle, they tend to become muscle cells, and on very rigid surfaces resembling bone, they differentiate into bone-producing osteoblasts.