You are an organized mass of 30 trillion cells, but these cells are in constant flux. Nearly 330 million new cells replace old cells in your body every day. Your intestinal lining renews itself every 3-5 days. Red blood cells die in just 120 days and so, are regularly replaced. This constant cycle of regeneration keeps you alive. Your skin remains intact, your blood flows uninterrupted, and your gut stands resilient in the face of harsh acids. None of this would be possible without a group of supercells in your body called stem cells. Over the last 50 years, we’ve uncovered some truly epic science surrounding these stem cells. Their regenerative abilities have brought them into focus as therapies for diseases, especially those of the blood. So, what are stem cells? How do they function? And how are they responsible for your existence, growth, and maintenance? Stem cells have two unique abilities that define them. Firstly, they can self-renew to create more stem cells, and secondly, they can differentiate into many different types of cells. Stem cells are crucially different from somatic cells in the body. Somatic cells—skin, muscle, fat, brain, or bone cells—cannot divide. A skin cell does not divide to form new skin cells. A skin cell simply gets old and dies. These types of cells are what we call ‘terminally differentiated’. Differentiation is a process through which a cell picks its fate, essentially choosing a career for the rest of their lives. Aren’t we lucky to have the option to quit our jobs whenever we want, and shift our lives in a new direction? We used to think differentiation was irreversible—a one-way street from a stem cell to a specialized cell. Essentially, we thought that a cell that becomes a skin cell will remain a skin cell forever. However, we were wrong, but more on that later. Stem cells have the ability to divide. An epithelial stem cell can divide into a new skin cell and another epithelial stem cell. The stem cells can also divide to make more stem cells. Therefore, an epithelial stem cell divides to self-renew and then differentiates into a skin cell. There are categories of stem cells based on the different cells into which they can differentiate. That measure is called the ‘potency’ or ‘potential’ of a stem cell. Totipotent stem cells are basically the MVPs of stem cells. They have nearly infinite dividing capabilities, allowing them to become any cell of an organism. The zygote, the single cell formed from the fusion of egg and sperm, is the OG totipotent stem cell. From its first few cell divisions arises a whole human. You stand today as an organized and systematic mass of trillions of cells arising from a single zygote. If you had to guess, how many cell types do you think an adult human has? Tell us in the comments below! There are also pluripotent stem cells to consider. Pluripotent stem cells are slightly more restricted than a zygote and can form almost all cell types. Embryonic stem cells or ESCs are a type of pluripotent stem cell that arise when the zygote divides to form a mass of cells called a blastocyst. When you restrict the fate of stem cells even further, they are called multipotent stem cells. These cells can differentiate into many different kinds of cells of a specific type. Hematopoietic stem cells in the bone marrow divide to make new blood cells—red blood cells, white blood cells, and platelets. The epithelial stem cells we mentioned earlier are another example. They can turn into any type of epithelial cell. Adults do retain some stem cells, which are present in particular niches to help maintain the body, replacing old cells with new ones. They can be multipotent stem cells, such as hematopoietic stem cells or unipotent stem cells. Unipotent stem cells can only differentiate into one type of cell, meaning that a muscle stem cell can only differentiate into a muscle cell. This raises an interesting question. All cells have the same DNA, so how are some cells stem cells and others not? And, as mentioned earlier, cell differentiation was assumed to be irreversible, but is that really true? Yes, cells all have the same DNA, but not all cells express all the genes. Genes are small sections of information in the DNA. Our more detailed video on DNA explains how the molecule works within a cell. Click the link in the top right corner to learn more. In brief, proteins in the cell read the information in a gene and convert that information into proteins the cell needs. The genes that are turned into proteins are the genes that are expressed. The cells switch off certain genes and are therefore not turned into proteins; we say that those genes are not expressed. Thus, a skin cell will only express genes, such as the gene for keratin, while a muscle cell won’t express that gene at all. In stem cells, this change in gene expression hasn’t happened yet and only occurs when the stem cell specializes. If we could change gene expression, maybe we could affect the identity of that cell? In 2006, researchers Shinya Yamanaka and Kazutoshi Takahashi did something researchers once thought impossible. They managed to convert a skin cell back into a pluripotent stem cell. They discovered 4 genes that controlled gene expression in cells, and when they introduced these genes in skin cells, some of them reverted to being stem cells! These cells are called induced pluripotent stem cells, aka iPSCs. The four factors that led to this discovery are called Yamanaka factors. In 2012, the researchers won a Nobel Prize for their work. Today, stem cells are used in many different therapies. Bone marrow transplants help patients with blood diseases regenerate healthy cells. Researchers use iPSCs to understand how organs and tissues of the body form. They hope to address questions related to development and cell differentiation and hopefully shed more light on congenital diseases. But, importantly, many of our body’s most critical and protective functions are only possible thanks to these powerful stem cells.