Stem cell biology is a tightly regulated process that begins during embryonic development and is present in the body in various forms through adulthood. Stem cells have the unique property of being self-renewing and either multipotent or pluripotent. Most cells in an organism are terminally differentiated, meaning that they no longer proliferate. On the other hand, pluripotent stem cells can differentiate into any tissue type (or divide to produce more stem cells, i.e., their self-renewing characteristic). Multipotent stem cells are adult stem cells that can differentiate into the terminally differentiated cells of a specific organ/tissue in which they reside.
During embryonic development, totipotent and pluripotent stem cells can both be found, depending on the stage of development. Totipotent stem cells are found immediately after the fusion of the sperm and egg. They only exist for the first few rounds of embryonic cell division and can develop into all differentiated cell/tissue types of the organism and the placenta. Pluripotent stem cells are first identified in the blastocyst stage in mammalian embryos and can develop into all differentiated cell/tissue types in an organism. The blastocyst's inner cell mass is comprised of these pluripotent stem cells.
In adulthood, somatic stem cell proliferation is a key process in recovery from tissue injury and disease. Not every adult organ contains stem cells, and this impacts the organ/tissue's ability to regenerate. Some adult organs that contain stem cells include the bone, skin, liver, intestine and skeletal muscle. Each of these niches contains stem cells that are partially differentiated, able to differentiate into organ-specific cell types. For example, hematopoietic stem cells (HSCs) are found in the bone marrow and can differentiate into all blood cell types1, whereas hepatic stem cells (i.e., oval cells or hepatocytes) have the potential to become either hepatocytes or cholangiocytes2. Furthermore, some organs, like the intestine, are frequently regenerating, while others, such as fat and muscle, can regenerate in response to tissue damage1.
Additionally, pluripotent stem cells can be laboratory-generated, and these cells are referred to as induced pluripotent stem cells, or iPSCs. Like somatic stem cells, iPSCs are typically engineered to regenerate the cell subsets of a particular organ. The factors responsible for the differentiation process are largely unique from organ to organ, although some common signaling pathways and downstream mediators do appear3. These include the Akt/AMPK axes, physical mediators of cell-cell contact such as adherens junctions and Wnt signaling, and metabolic changes.
