Common questions in molecular biology: What are types of cell-cell interactions?

Much like bees or ants, cells are inherently social. Also like various hive-based insects, the social nature of the interactions are important for dictating function and well being of the whole.

Since cells lack the ability to do a waggle dance (a key method bees use for communicating the location of flowers to each other), they must rely on a variety of cell-cell interactions for communication instead.

In this Common questions in molecular biology blog post, I explore the nature of cell-cell interactions. I’ll start with a description of what we mean by cell-cell interactions, before giving examples of three common types of such interactions, including direct physical contact, cell signaling interactions, and the cell-cell interactions that underlie immune system function. I’ll also discuss why studying cell-cell interaction is important for understanding our overall biology and disease processes. Throughout, I’ll also highlight how cell-cell interactions can be studied using single-cell sequencing and NanoString’s CosMx™ Spatial Molecular Imager.

What are some examples of cell-cell interactions?

Any time cells communicate with one another, it is considered a type of cell-cell interaction. There are many different types of cell-cell interactions. For example, physical contact is a type of cell-cell interaction that impacts cellular behavior. Typically, cells do not continue to divide and produce more cells once they are in physical contact with one another. This phenomenon is called growth inhibition. Escaping from growth inhibition and consequently beginning to grow out of control is a hallmark of cancer development.

Cell-cell interaction can also occur through ligand-receptor interactions. This is commonly part of a phenomenon called cell signaling. Cell signaling can occur between cells that are close to one another (paracrine signaling) or cells that are far away from each other (endocrine signaling).

In this type of cell-cell interaction, one cell produces a ligand. This ligand then goes and binds to a receptor on a target cell. Ligands are very specific to their receptors, similar to how a key corresponds to a lock. Once the ligand binds to the receptor, the signal is transduced between cells. The ultimate result is a biological change in the target cell. For example, many cell signaling pathways ultimately cause changes in gene expression. There are many kinds of cell signaling pathways, such as g-protein coupled receptor (GPCR) signaling. Humans have over 800 known GPCRs. These GPCRs are very common drug targets. GPCRs mediate a wide variety of processes, such as smell and response to light. GPCRs are also implicated in the development of cancer.

Cell-cell interactions can also occur between static and mobile cells. For example, many immune cells circulate throughout the body in the bloodstream. These cells have various functions in order to protect the body from outside threats. In the case of a microbial invader, infected cells will secrete chemicals like histamines. White blood cells like macrophages recognize these chemicals and will move into the area and engulf damaged cells and/or microbial particles. This process is part of our innate immune system.

We also have an acquired immune system. For example, antigen-presenting complexes that identify cancerous cells and present parts of cancer cells to T cells. The T cells become activated and then recognize and bind to cancer cells, working to destroy them. This type of cell-cell interaction is important for ridding the body of cancer.

Understanding what is occurring at the genomic level of these individual cells is an important application for single-cell signaling. For example, researchers are using NanoString’s CosMx™ Spatial Molecular Imager to specifically investigate the individual cells at this crucial boundary. This kind of work, especially combined with innovations in Chimeric Antigen Receptor (CAR) T cell therapy, a type of genetic engineering, could lead to substantial improvements in our understanding of cancer biology and future treatments.

Why is studying cell-cell interaction important?

In order for our bodies to function effectively, all 37.2 trillion of our cells need to coordinate their function. Therefore, there must be cell-cell interactions. For example, to maintain homeostasis, our cells provide checks and balances on one another. If a cell or neighboring cell detects that something is dysfunctional with a cell, the cell can be triggered to undergo programmed cell death or apoptosis. Inability to undergo this process can contribute to the development of diseases, such as cancer.

One can imagine that a significant amount of coordination goes into getting trillions of cells to work together. Coordination between cells is also mediated through cell-cell interactions. For example, wound healing is an important function of various cell types working together in tissues. Upon injury, a suite of cellular processes involving a wide variety of cells begin. First, clotting is initiated to stop bleeding, which at its core is the loss of cells from the body. Inflammatory processes also begin, which recruit immune cells to the site. The immune cells hedge against potential microbial invaders to protect the rest of the body. After this initial response, new blood and skin cells begin to form and differentiate appropriately to begin to close and repair the wound.

Wound healing involves a variety of cell-cell interactions across a variety of cell and tissue types. Some of these cells, like skin cells, are relatively rare. Therefore, single-cell sequencing using NanoString’s CosMx SMI is particularly useful for uncovering the spatial and genomic dynamics that occur during wound healing. This will be particularly advantageous for identifying treatments for people who have difficulties with wound healing, such as diabetics.

Understanding cell-cell interactions is important for preventing disease and maintaining homeostasis

In order for the body to function, all 37.2 trillion cells that make up the body must coordinate with one another. There are a variety of types of cell-cell interactions that help all cells in the body to work together as a whole. These include direct physical contact, cell signaling, and the action of the immune system.

Given the importance of cell-cell interactions to both our basic biology and the development of disease processes, single-cell sequencing using the CosMx Spatial Molecular Imager is an excellent tool for providing new insights into cell-cell interactions. These new insights into the genomic and spatial principles that govern cell function are exciting and could lead to new treatments for devastating disease such as cancer.

The CosMx™ SMI and decoder probes are not offered and/or delivered to the Federal Republic of Germany for use in the Federal Republic of Germany for the detection of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinations thereof in a method used in fluorescence in situ hybridization for detecting a plurality of analytes in a sample without the consent of the President and Fellows of Harvard College (Harvard Corporation) as owner of the German part of EP 2 794 928 B1. The use for the detection of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinations thereof is prohibited without the consent of the President and Fellows of Harvard College (Harvard Corporation).