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I am trying to model bone remodeling process and I wonder what is the difference between phenotype switching and differentiation. I am relatively inexperienced in biology. Please explain me with examples related to this context. Thanks in advance.

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Differentiation is a process which occurs in multiple steps. A precursor cell for example a mesenchymal stem cell can proliferate (divide/multiple). The stem cell can commit to become a progenitor cell (osteoprogenitor cell) which can still proliferate but has acquired the possibility to differentiate to a different cell type. In some cases or when specific conditions are met,the progenitor can differentiate to a pre-osteoblast and finally to a mature osteoblast.

The differentiation process require the activation of a specific transcription program and leads to large changes in the cell like morphology, size, and function. Once differentiated, the cell cannot proliferate anymore and loss the capacity to divide.

Phenotype switching can be broadly defined as any change in the phenotype like morphological change, expression of specific biomarkers, etc. In the context of differentiation phenotype switching refers to the acquisition of a specific differentiation marker usually a transcription marker like Runx2. While they might not be a large morphological change, the fact that the cell express this transcription factor indicates it is switching phenotypes and starting differentiation.

In summary: differentiation is process which occurs in multiple distinct steps. Differentiated states are characterized by a specific morphology, acquisition of key bio markers (usually transcription factors), loss of the capacity to proliferate, and a cellular specific function. Phenotype switching refers to the time frame when a cell changes from one phenotype to another; when it acquires or loss a defined morphological state or key markers.

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  • $\begingroup$ Both differentiation and phenotype switching are terms which are used in intense research areas. Their definition will get revised in the next decade for sure. The definitions I have highlighted are what you will classically find in most publications but in reality it is difficult to define specific steps in a differentiation process because it is usually a continuous process. Phenotype switching is even worse to define as it assumes that once classified to a category a cell does not have a dynamic phenotype: a cell which proliferate change phenotype as it goes through the cell cycle. $\endgroup$ – Dr. H. Lecter Aug 23 at 7:33
  • $\begingroup$ Thank you very much for the response. Differentiated cells lose the ability to proliferate. Does that mean they don't divide forever? Do they die? $\endgroup$ – Tarun Sai Aug 23 at 12:56
  • $\begingroup$ Technically yes they should not divide. Theoretically, these cells could accumulate genomic mutation (UV, chemical environment, etc) and become cancerous but I'm unsure if this has been convincingly shown in the literature. Yes differentiated cells can die by different mechanisms including apoptosis and necrosis, and be replaced by others cells. A good example would be neuronal cells. $\endgroup$ – Dr. H. Lecter Aug 23 at 13:10

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