Stem Cells: Self-Renewal, Differentiation, and Heterogeneity

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Stem Cells: Self-Renewal, Differentiation, and Heterogeneity

Joe Buran, Nick Rotella, Karamveer Birthare

Introduction- Stem cells are biological cells found in all multi-cellular organisms, and have the potential to develop into several different types of cells in the body during their early life and throughout growth.  They also play a major role in the regeneration of many tissues, as they continue to divide almost without limit as long as the organism is still alive.  After a stem cell divides, it can either remain a stem cell or continue to grow, or it can differentiate into a more specific cell with a specialized function.

Heterogeneity of Stem Cells- The classical definition of a stem cell requires that it possesses two properties, or metastable cell states. The first property, self-renewal, means that they have the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Secondly, they must possess potency. This is the ability under certain physiological conditions to become, or differentiate, into tissue or organ-specific cells with defined tissues. However, in other areas and tissues of the body, stem cells may only divide under special biological conditions. The ability of a stem cell to maintain both metastable cell states is referred to as stem cell heterogeneity. Various groups of scientists have identified specific transcription factors that maintain a stem cell's self-renewal abilities. Expression of these transcription factors fluctuate in response to extracellular stimuli, thus directing which metastable cell state the stem cell is currently in. For example, the transcription factor Nanog pertains to a stem cell's self-renewal ability. Expression of Nanog is shown in two forms, positive and negative. Positive Nanog shows a higher propensity for self-renewal and negative Nanog shows a higher propensity for differentiation. Nanog expression can be controlled using extracellular stimuli and shifted between positive and negative expression types. This ability of the stem cell to be shifted between both expression types depending on extracellular stimuli therefore proves the existence of heterogeneity in stem cells. Along with Nanog, other important transcription factors that help maintain a stem cell’s self-renewal ability include Oct4, Klf4, and Sox2.

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        There are 3 major types of stem cells scientists use today – embryonic, ‘somatic’ or ‘adult’ stem cells, and induced pluripotent stem cells (iPSC’s).  The uniqueness of stem cells and their self-renewal and regenerative abilities provide incredible potential for advancements in the field of regenerative medicine.  However, a lot of work still remains to be performed and studied in order to fully understand these unique cells and reach the full potential of their use.  Researchers hope that one day stem cells can be used to treat various diseases such as diabetes and heart disease.  

Self-Renewal of Stem Cells- ...

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